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Abstract Background Chronic empyema after total pneumonectomy is a potentially fatal complication.The aim of the study is to explore the treatment strategy and clinical efficacy of chronic empyema after pneumonectomy. Methods A retrospective analysis of 6 patients with chronic empyema after pneumonectomy in our hospital. Utilizing a staged surgical model, the treatment approach involved rib debridement drainage, open-window thoracostomy (OWT), and the application of autologous tissue flaps, including free myocutaneous flap, pedicled muscle flap, and pedicled greater omentum, to effectively eliminate the abscess cavity. Results All patients with empyema were successfully treated after surgery, with follow-up durations ranging from 3 to 29 months and an average of (10.50 ± 9.67) months. Re-examination using chest computed tomography (CT) or magnetic resonance imaging (MRI) revealed that the empyema residual cavity had either completely disappeared or had significantly reduced. Conclusion The treatment of chronic refractory empyema after total pneumonectomy by rib debridement drainage, OWT and autologous tissue flap transplantation has a high cure rate and satisfactory clinical effect.

The regulation of the cell cycle is essential for maintaining normal cellular function, especially in the development of diseases such as lung cancer. The cell cycle consists of four major phases (G1, S, G2 and M phases), which are characterized by a series of precise molecular events to ensure proper cell proliferation and division. In lung cancer cells, cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells. G2 and S-phase expressed 1 (GTSE1) is a regulatory protein found in the cytoplasm of the cell, which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis. GTSE1 affects cell cycle progression by interacting with cyclin-dependent kinase inhibitor 1A (p21) and maintaining the stability of p21, which in turn inhibits the activity of cyclin-dependent kinase 1/2 (CDK1/2). In addition, GTSE1 is also involved in the regulation of tumor protein 53 (p53) signaling pathway. With the assistance of mouse double minute 2 homolog (MDM2), GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation, thus affecting cell cycle and cell death-related signaling pathways. This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer, as well as its potential mechanisms involved in cell cycle regulation.

Background CameL phase 3 study demonstrated the superiority of camrelizumab plus chemotherapy over chemotherapy alone for progression-free survival in patients with previously untreated advanced non-squamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. Here, we present the 5-year outcomes.Methods Patients were randomized (1:1) and received 4–6 cycles of camrelizumab plus carboplatin and pemetrexed (n=205) or carboplatin and pemetrexed (n=207) every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only. Crossover from chemotherapy group to camrelizumab monotherapy was permitted after disease progression.Results Median time from randomization to data cut-off was 65.2 months (range, 59.7–72.2). HR for overall survival (OS) was 0.74 (95% CI 0.58 to 0.93; one-sided p=0.0043), and was 0.62 (95% CI 0.49 to 0.79; one-sided p

Background Serum neuron-specific enolase (NSE) had been associated with survival of several cancers. However, its prognostic significance for colorectal cancer (CRC) has not been effectively discussed. We aimed to investigate the relationship between baseline serum NSE and the overall survival (OS) of colorectal adenocarcinoma (CRAD) patients. Methods A retrospective study had been conducted by including 564 histopathology confirmed CRAD patients between January 2013 and December 2018 from Yunnan Provincial Cancer hospital, China. Cox proportional hazards model was used to estimate the crude and adjusted associations between serum NSE measured at diagnosis and the OS of the patients. Restricted cubic spline (RCS) was further applied to delineate dose-response trend of the NSE-OS association. Results After controlling for possible confounding factors, baseline serum NSE was significantly associated with OS in CRAD: when dichotomizing by the median, patients with higher baseline serum NSE (NSE >= 12.93 ng/mL) were observed a worse prognosis (hazard ratio, HR: 1.82, 95% CI [1.30–2.55], p < 0.01). Stratified analysis by tumor stage revealed a stronger NSE-OS association in advanced CRAD patients. RCS disclosed a prominent dose-response relationship in NSE-OS association for all CRAD patients: along with the increase of baseline serum NSE, the adjusted HR of CRAD patients increased gradually. This dose-response trend is also evident in advanced stage CRAD patients, but not in early stage CRAD patients. Conclusions Serum NSE measured at diagnosis might be a useful prognostic indicator for CRAD, especially for advanced stage patients.

Abstract Background Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. Methods In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT–PCR) in peripheral TCL patients. Results RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. Conclusion Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

Invasion and migration are the primary factors for mortality in lung adenocarcinoma (LUAD) patients. The precise role of RNA-binding motif protein15 (RBM15)-mediated m6A modification in LUAD is not yet fully clarified. This research aims to elucidate the mechanism of RBM15 in the invasion and migration of LUAD.Western blot and dot blot assay results showed that RBM15 and methylation levels of m6A were highly expressed in LUAD tissues. Overexpression of RBM15 by lentivirus transfection increased m6A levels and promoted the invasion, migration, and proliferation of A549 and H1734 cells. Knockdown of RBM15 by lentivirus transfection had opposite effects on m6A levels, invasion, migration, and proliferation of A549 and H1734 cells. The results of nude mouse proliferation models confirmed that RBM15 knockdown inhibited in vivo tumor proliferation . Sequencing and immunoprecipitation identified RASSF8 as an interacting protein of RBM15 involved in cell invasion and migration. RBM15-mediated m6A modification inhibited RASSF8 protein levels and increased LUAD cell invasion and migration. The rescue assays demonstrated that the regulation of RBM15 on LUAD cell invasion and migration was partially rescued by RASSF8.In conclusion, RBM15-mediated m6A modification inhibits the RASSF8 protein levels and increases cell invasion and migration. Thus, targeting the RBM15-m6A-RASSF8 axis may be a promising strategy for repressing LUAD cell invasion and migration.

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.

Lung cancer associated with cystic airspaces (LCCA) is a type of lung cancer characterized by the presence of cystic cavities in or around the tumor on imaging. Due to its high potential for misdiagnosis or underdiagnosis, the prognosis of LCCA patients is poor, necessitating further large-scale clinical studies to elucidate its characteristics. Currently, four imaging classification systems exist, and there has been a progressive increase in attention towards LCCA, particularly with regard to the study of its imaging features. The results indicate a correlation between the pathological features and imaging findings of LCCA; however, research on driver gene mutations and molecular subtyping associated with lung cancer remains insufficient. Due to the challenges associated with early diagnosis and the poorer prognosis compared to general types of lung cancer, this paper comprehensively reviews the research progress on LCCA, including its definition, etiology, pathogenesis, imaging features, histological and pathological features, treatment, and prognosis, aiming to serve as a valuable resource for clinical decision-making.

Abstract At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably and eventually progress into different types of diabetes complications, resulting in poor quality of life. Unfortunately, the clear etiology and pathogenesis of diabetes complications have not been elucidated owing to intricate whole‐body systems. The immune system was responsible to regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary to diabetes complications. In fact, previous studies have been shown inflammation plays multifunctional roles in the pathogenesis of diabetes complications and is attracting attention to be the meaningful therapeutic strategy. To this end, this review systematically concluded the current studies over the relationships of susceptible diabetes complications (e.g., diabetic cardiomyopathy, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic nephropathy) and inflammation, ranging from immune cell response, cytokines interaction to pathomechanism of organ injury. Besides, we also summarized various therapeutic strategies to improve diabetes complications by target inflammation from special remedies to conventional lifestyle changes. This review will offer a panoramic insight into the mechanisms of diabetes complications from an inflammatory perspective and also discuss contemporary clinical interventions.

Abstract Background Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. Methods We extracted age-specific rate of cancer cases and deaths during 2007–2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007–2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). Results In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7–4.3%) during 2007–2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3–4.9%), 3.3% (95% CI: 2.6–4.1%), 2.4% (95% CI: 1.4–3.5%), 4.4% (95% CI: 2.5–6.4%), and 3.6% (95% CI: 1.4–5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007–2030, except that uterine cancer deaths and mortality were declined. Conclusions With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned.

Abstract In minimally invasive thoracoscopic surgery, for solitary pulmonary nodules (SPNs) far from the pleura, it is difficult to resected by only relying on imaging data, and effective preoperative localization can significantly improve the success rate of surgery. Therefore, preoperative localization is particularly important for accurate resection. Here, we compare the value of a novel Lung‐pro‐guided localization technique with Hook‐wire localization in video‐assisted thoracoscopic surgery. Method In this study, 70 patients who underwent CT‐guided Hook‐wire localization and Lung‐pro guided surgical marker localization before VATS‐based SPNs resection between May 2020 and March 2021 were analyzed, and the clinical efficacy and complication rate of the two groups were compared. Result Thirty‐five patients underwent Lung‐pro guided surgical marker localization, and 35 patients underwent CT‐guided Hook‐wire localization. The localization success rates were 94.3% and 88.6%, respectively (p = 0.673). Compared with the puncture group, the locating time in the Lung‐pro group was significantly shorter (p = 0.000), and the wedge resection time was slightly shorter than that in the puncture group (P = 0.035). There were no significant differences in the success rate of localization, localization complications, intraoperative blood loss, postoperative hospital stay, and the number of staplers used. Conclusion The above studies show that the Lung‐pro guided surgical marker localization and the CT‐guided Hook‐wire localization have shown good safety and effectiveness. However, the Lung‐pro guided surgical marker localization may show more safety than the Hook‐wire and can improve the patient's perioperative experience.

Abstract Background Although surgery has been widely applied for SPLC therapy, there is still no uniform treatment approach. Whether SPLC and primary lung cancer have similar prognostic characteristics remains controversial. Herein, based on a systematic review and meta-analysis, we aimed to enucleate the influences of diverse surgical strategies and underlying prognostic factors on the prognosis of patients with both the first primary lung cancer and SPLC underwent surgical resection. Methods A comprehensive and systematic literature search was implemented in three databases (MEDLINE, EMBASE, and Cochrane), and eligible studies were screened following inclusion and exclusion criteria. Meanwhile, we extracted the hazard ratios (HR) together with 95% confidence intervals (CI) for each prognostic factor, either directly or indirectly, from the enrolled literature. Results Eleven studies (published between 2000 and 2022) were included in this study, including 1,131 SPLC patients. The overall survival (OS) exhibited no difference between patients with lobectomy and sublobar resection after SPLC (HR: 0.87, 95%CI: 0.62–1.21, P = 0.41). The patients after completion pneumonectomy had a poor prognosis (HR: 1.85, 95% CI: 1.34–2.55, P 2 cm (HR: 2.44, 95%CI: 1.73–3.44, P 2 cm, solid predominant in CT morphology, lymph node metastasis, and smoking had a poor prognosis. Meanwhile, SPLC has similar prognostic characteristics with single primary lung cancer. However, the study has some limitations and more evidence is warranted to verify the findings.

Lung cancer is the leading cause of cancer death in the world today, and adenocarcinoma is the most common histopathological type of lung cancer. In May 2021, World Health Organization (WHO) released the 5th edition of the WHO classification of thoracic tumors, which classifies invasive non-mucinous adenocarcinoma (INMA) into lepidic adenocarcinoma, acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma, and micropapillary adenocarcinoma based on its histological characteristics. These five pathological subtypes differ in clinical features, treatment and prognosis. A complete understanding of the characteristics of these subtypes is essential for the clinical diagnosis, treatment options, and prognosis predictions of patients with lung adenocarcinoma, including recurrence and progression. This article will review the grading system, morphology, imaging prediction, lymph node metastasis, surgery, chemotherapy, targeted therapy and immunotherapy of different pathological subtypes of INMA.

Abstract Background Although programmed cell death 1 (PD‐1) blockade plus chemotherapy can significantly prolong the progression‐free survival (PFS) and overall survival (OS) in first‐line settings in patients with driver‐negative advanced non‐small‐cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD‐1 blockade plus chemotherapy. Methods Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD‐1 ligand (PD‐L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan‐Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. Results Responders had significantly higher CD8/PD‐L1 (P = 0.015) or CD68/PD‐L1 co‐expression levels (P = 0.021) than non‐responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD‐L1 or CD68/PD‐L1 co‐expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co‐expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD‐L1 co‐expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co‐expression subgroups. The predictive value of CD8/PD‐L1 and CD68/PD‐L1 co‐expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD‐L1 or CD68/PD‐L1 co‐expression, the positive groups had a significantly higher proportion of TP53/KRAS co‐mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD‐L1 co‐expression group. Conclusion Tumor immune microenvironmental marker expression, especially CD8/PD‐L1 or CD68/PD‐L1 co‐expression, was associated with the efficacy of PD‐1 blockade plus chemotherapy as first‐line treatment in patients with advanced NSCLC.

ImportancePatients with EGFR mutations who have advanced-stage non-small cell lung cancer (NSCLC) already receive tyrosine kinase inhibitors (TKIs) as the standard first-line therapy. Notably, Yunnan is a regional high incidence area of lung cancer in the highlands with a high rate of rare EGFR mutations. Overall, lung cancer patients in Xuanwei may present a distinct subgroup globally. Recent studies suggested that the NSCLC cohort in Xuanwei harbored a significantly higher uncommon mutation rate. However, little was known about the clinicopathological features and treatment efficacy of EGFR-TKI in Yunnan NSCLC patients.ObjectiveThis study aimed to investigate the clinical impact of histologic type on the survival outcomes of patients with stage IIIB and IV NSCLC receiving EGFR-TKI treatment of Yunnan in southwestern China.MethodsIn this retrospective study, we enrolled advanced NSCLC patients (IIIB-IV) with EGFR mutations who were first diagnosed and treated at Yunnan Cancer hospital from January 2016 to December 2019. Sociodemographics, lifestyle, survival, and clinicopathological characteristics of the patients were collected. The Kaplan-Meier method was used to assess the OS and PFS of patients. An analysis of prognostic factors was conducted using Cox regression.ResultsA total of 468 eligible patients were included. The median progression-free survival (PFS) and overall survival(OS) were 11.30(95% CI, 10.12-12.48) months and 30.30(95% CI, 26.24-34.36) months. Based on survival analysis among all the patients,females(HR=0.815;95% CI:0.671-0.989; P=0.017), Xuanwei origin (HR=0.776; 95% CI: 0.609-0.989; P=0.040), sample types(HR=0.780; 95% CI: 0.642-0.947; P=0.012) had a longer PFS. Multivariable analysis showed that only the sample type was an independent factor on median PFS with EGFR-TKI therapy. Patients less than 60 years old (HR=1.433; 95% CI:1.134-1.812, P=0.003)had better OS, but objectives with BMI≥24kg/m2(HR=0.653; 95% CI: 0.500-0.864; P=0.002), females(HR=0.776; 95% CI:0.613-0.982; P=0.035)and patients with tissue sample type (HR=0.760; 95% CI:0.600-.0961; P=0.022) had better OS. Notably, subgroup analysis of our study also found that PFS was significantly better in patients with G719X, L861Q, S768I, G719X+L861Q, and G719X+S768I in Xuanwei than classical mutation ones, including 19-Del and L858R (median 22.7 vs. 12.0 months, HR=0.523, P=0.010), while PFS was inferior in patients with rare mutations of EGFR in non-Xuanwei than the classical mutation ones (median 5.10 vs. 11.10 months, HR=1.760, P=0.015).ConclusionNSCLC patients in Yunnan displayed a unique EGFR mutation profile, especially a higher prevalence of EGFR uncommon and compound mutations subtype. This study indicates prognostic factors of NSCLC treated with EGFR-TKI in Yunan and Xuanwei. This study will provide new clinical evidence for EGFR-TKI-targeted therapy in patients with rare EGFR mutations in China and worldwide. More researchs were needed for NSCLC EGFR-TKI therapy and medical insurance policy-making in Yunnan, Xuanwei area and uncommon especially.

Background: Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden linked to lung cancer. In Xuanwei, China, lung cancer rate for nonsmoking women is among the highest in the world and largely attributed to high levels of polycyclic aromatic hydrocarbons (PAHs) that are produced from combustion of smoky (bituminous) coal used for cooking and heating. Epigenetic age acceleration (EAA), a DNA methylation-based biomarker of aging, has been shown to be highly correlated with biological processes underlying the susceptibility of age-related diseases. We aim to assess the association between HAP exposure and EAA. Methods: We analyzed data from 106 never-smoking women from Xuanwei, China. Information on fuel type was collected using a questionnaire, and validated exposure models were used to predict levels of 43 HAP constituents. Exposure clusters were identified using hierarchical clustering. EAA was derived for five epigenetic clocks defined as the residuals resulting from regressing each clock on chronological age. We used generalized estimating equations to test associations between exposure clusters derived from predicted levels of HAP exposure, ambient 5-methylchrysene (5-MC), a PAH previously found to be associated with risk of lung cancer, and EAA, while accounting for repeated-measurements and confounders. Results: We observed an increase in GrimAge EAA for clusters with 31 and 33 PAHs reflecting current (β = 0.77 y per standard deviation (SD) increase, 95 % CI:0.36,1.19) and childhood (β = 0.92 y per SD, 95 % CI:0.40,1.45) exposure, respectively. 5-MC (ng/m3-year) was found to be associated with GrimAge EAA for current (β = 0.15 y, 95 % CI:0.05,0.25) and childhood (β = 0.30 y, 95 % CI:0.13,0.47) exposure. Conclusions: Our findings suggest that exposure to PAHs from indoor smoky coal combustion, particularly 5-MC, is associated with GrimAge EAA, a biomarker of mortality.

Abstract The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assays were adopted to validate the interaction among Mxi1, miR-300 and KLF9. Loss- and gain-of-function studies were conducted to determine the roles of Mxi1, miR-300, and KLF9 in cell proliferation, migration, and invasion in vitro and their effects on myeloid-derived suppressor cell (MDSC) recruitment in vivo. Mxi1 was poorly expressed in lung cancer tissues and cells and its poor expression was associated with poor prognosis. Mxi1 inhibited miR-300 by suppressing its transcription. miR-300 suppressed the expression of KLF9, and KLF9 negatively regulated GADD34 expression in lung cancer cells. Mxi1 or KLF9 elevation or miR-300 repression inhibited lung cancer cell proliferation, as evidenced by reduced Ki67 and PCNA expression, and lowered invasion and migration. In vivo findings revealed that silencing KLF9 induced tumor growth by enhancing MDSC-mediated immunosuppression through upregulation of GADD34. Collectively, these findings suggest that Mxi1 can inhibit lung cancer progression by regulating the miR-300/KLF9 axis and GADD34-mediated immunosuppression.

Abstract Lung cancer is the highest incidence and mortality of all cancers around the world. In the present immunotherapy era, an increasing number of immunotherapeutic agents including monoclonal antibody‐targeted drugs have been used in the clinical treatment of malignancy, but it still has many limitations. Chimeric antigen receptor‐modified T (CAR‐T) cells, a novel adoptive immunotherapy strategy, have not only been used successfully against hematological tumors, but have also opened up new avenues for immunotherapy of solid tumors, including lung cancer. However, targeting lung cancer‐specific antigens using engineered CAR‐T cells is complicated by the lack of proper tumor‐specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR‐T cell infiltration into tumor tissues, along with off‐target effect, etc. Simultaneously, the clinical application of CAR‐T cells remains limited because of many challenges such as tumor lysis syndrome, neurotoxicity syndrome, and cytokine release syndrome. In this review, we outline the basic structure and generation characteristic of CAR‐T cells and summarize the common tumor‐associated antigens in clinical trials of CAR‐T cell therapy for lung cancer, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for the pre‐clinical experiments and clinical trials of CAR‐T cell therapy in lung cancer.

Abstract The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated. It is believed that DNA replication initiates from open chromatin domains; thus, replication origins reside in open and active chromatin. However, we report here that lysine-specific demethylase 1 (LSD1), which biochemically catalyzes H3K4me1/2 demethylation favoring chromatin condensation, interacts with the DNA replication machinery in human cells. We find that LSD1 level peaks in early S phase, when it is required for DNA replication by facilitating origin firing in euchromatic regions. Indeed, euchromatic zones enriched in H3K4me2 are the preferred sites for the pre-replicative complex (pre-RC) binding. Remarkably, LSD1 deficiency leads to a genome-wide switch of replication from early to late. We show that LSD1-engaged DNA replication is mechanistically linked to the loading of TopBP1-Interacting Checkpoint and Replication Regulator (TICRR) onto the pre-RC and subsequent recruitment of CDC45 during origin firing. Together, these results reveal an unexpected role for LSD1 in euchromatic origin firing and replication timing, highlighting the importance of epigenetic regulation in the activation of replication origins. As selective inhibitors of LSD1 are being exploited as potential cancer therapeutics, our study supports the importance of leveraging an appropriate level of LSD1 to curb the side effects of anti-LSD1 therapy.

ObjectivesLung cancer has been widely characterized through radiomics and artificial intelligence (AI). This review aims to summarize the published studies of AI based on positron emission tomography/computed tomography (PET/CT) radiomics in non-small-cell lung cancer (NSCLC).Materials and methodsA comprehensive search of literature published between 2012 and 2022 was conducted on the PubMed database. There were no language or publication status restrictions on the search. About 127 articles in the search results were screened and gradually excluded according to the exclusion criteria. Finally, this review included 39 articles for analysis.ResultsClassification is conducted according to purposes and several studies were identified at each stage of disease:1) Cancer detection (n=8), 2) histology and stage of cancer (n=11), 3) metastases (n=6), 4) genotype (n=6), 5) treatment outcome and survival (n=8). There is a wide range of heterogeneity among studies due to differences in patient sources, evaluation criteria and workflow of radiomics. On the whole, most models show diagnostic performance comparable to or even better than experts, and the common problems are repeatability and clinical transformability.ConclusionAI-based PET/CT Radiomics play potential roles in NSCLC clinical management. However, there is still a long way to go before being translated into clinical application. Large-scale, multi-center, prospective research is the direction of future efforts, while we need to face the risk of repeatability of radiomics features and the limitation of access to large databases.

Background: We previously showed that exposure to 5-methylchrysene (5MC) and other methylated polycyclic aromatic hydrocarbons (PAHs) best explains lung cancer risks in a case-control study among non-smoking women using smoky coal in China. Time-related factors (e.g., age at exposure) and non-linear relations were not explored. Objective: We investigated the relation between coal-derived air pollutants and lung cancer mortality using data from a large retrospective cohort. Methods: Participants were smoky (bituminous) or smokeless (anthracite) coal users from a cohort of 42,420 subjects from four communes in XuanWei. Follow-up was from 1976 to 2011, during which 4,827 deaths from lung-cancer occurred. Exposures were predicted for 43 different pollutants. Exposure clusters were identified using hierarchical clustering. Cox regression was used to estimate exposure–response relations for 5MC, while effect modification by age at exposure was investigated for cluster prototypes. A Bayesian penalized multi-pollutant model was fitted on a nested case-control sample, with more restricted models fitted to investigate non-linear exposure–response relations. Results: We confirmed the strong exposure–response relation for 5MC (Hazard Ratio [95% Confidence Interval] = 2.5 [2.4, 2.6] per standard-deviation (SD)). We identified four pollutant clusters, with all but two PAHs in a single cluster. Exposure to PAHs in the large cluster was associated with a higher lung cancer mortality rate (HR [95%CI] = 2.4 [2.2, 2.6] per SD), while exposure accrued before 18 years of age appeared more important than adulthood exposures. Results from the multi-pollutant model identified anthanthrene (ANT) and benzo(a)chrysene (BaC) as risk factors. 5MC remained strongly associated with lung cancer in models that included ANT and BaC and also benzo(a)pyrene (BaP). Conclusion: We confirmed the link between PAH exposures and lung cancer in smoky coal users and found exposures before age 18 to be especially important. We found some evidence for the carcinogen 5MC and non-carcinogens ANT and BaC.

Patients with advanced esophageal cancer have poor prognosis and limited treatment options. This randomized, phase II trial compares the efficacy and safety of the anti-PD-1 antibody sintilimab versus chemotherapy in Chinese patients with esophageal squamous cell carcinoma after first-line therapy

Abstract Background Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. Methods Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. Results Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. Conclusion On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. Trial registration ClinicalTrials.gov identifier: NCT03668496.

Abstract Background Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. Methods A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. Results The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67–0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR

BackgroundChina’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.MethodsTissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.ResultsIn cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P

The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In this study, we evaluated the safety and immunogenicity of a newly developed DTacP-sIPV-Hib combination vaccine in animal models. We used 40 mice and 46 cynomolgus monkeys to evaluate acute and long-term toxicity. Thirty-six guinea pigs were used for sensitization assessment. For immunogenicity assessment, 50 NIH mice and 50 rats were equally randomized to receive 3 doses of 3 different batches of the tested vaccine at an interval of 21 d, or physiological saline solution (0.5 mL). Orbital blood was collected at an interval of 21 d post inoculation to detect related antibody titers or neutralizing antibody titers against poliovirus. Gross autopsy and histopathological examination revealed no abnormal toxicity or irritation in mice and cynomolgus monkeys. Sensitization assessment in guinea pigs indicated the lack of evident allergic symptoms in the high- and low-dose vaccine groups within 30 min after repeated stimulation. The DTacP-sIPV-Hib combination vaccine induced significant immune responses in mice, rats, and cynomolgus monkeys, with 100% seroconversion rates after 3 doses. The DTacP-sIPV-Hib combination vaccine is safe and immunogenic in animal models. Three doses of the vaccine elicited satisfactory antibody responses in mice, rats, and cynomolgus monkeys.

Abstract The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC.Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1.In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.

Objectives Never-smoking women in Xuanwei (XW), China, have some of the highest lung cancer rates in the country. This has been attributed to the combustion of smoky coal used for indoor cooking and heating. The aim of this study was to evaluate the spectrum of cause-specific mortality in this unique population, including among those who use smokeless coal, considered ‘cleaner’ coal in XW, as this has not been well-characterised.Design Cohort study.Setting XW, a rural region of China where residents routinely burn coal for indoor cooking and heating.Participants Age-adjusted, cause-specific mortality rates between 1976 and 2011 were calculated and compared among lifetime smoky and smokeless coal users in a cohort of 42 420 men and women from XW. Mortality rates for XW women were compared with those for a cohort of predominately never-smoking women in Shanghai.Results Mortality in smoky coal users was driven by cancer (41%), with lung cancer accounting for 88% of cancer deaths. In contrast, cardiovascular disease (CVD) accounted for 32% of deaths among smokeless coal users, with 7% of deaths from cancer. Total cancer mortality was four times higher among smoky coal users relative to smokeless coal users, particularly for lung cancer (standardised rate ratio (SRR)=17.6). Smokeless coal users had higher mortality rates of CVD (SRR=2.9) and pneumonia (SRR=2.5) compared with smoky coal users. These patterns were similar in men and women, even though XW women rarely smoked cigarettes. Women in XW, regardless of coal type used, had over a threefold higher rate of overall mortality, and most cause-specific outcomes were elevated compared with women in Shanghai.Conclusions Cause-specific mortality burden differs in XW based on the lifetime use of different coal types. These observations provide evidence that eliminating all coal use for indoor cooking and heating is an important next step in improving public health particularly in developing countries.

Background: Linc00996 has been reported in a variety of malignant tumors, but its potential role and significance in lung adenocarcinoma (LUAD) are not fully understood. The authors investigated the expression and biological behavior of Linc00996 in LUAD and elucidated the function of its potential target genes.Materials and methods: The data of Linc00996 expression in cancers were derived from GEPIA. GEO and TCGA datasets were used to identify the differential expression of Linc00996 in LUAD and analyze the respective correlation between different expression levels and LUAD stage and survival prognosis. We further elucidated the potential biological processes and pathways involved with Linc00996 in LAUD by GSEA. ssGSEA was applied to explore the relationship between Linc00996 and immune activity. Finally, the clinical impact of Linc00996 was assessed in 61 patients with LUAD, and the biological functions of Linc00996 were determined by a series of experiments in vitro, such as CCK8, colony formation, migration, and invasion assays.Results: Compared with adjacent normal lung tissues, Linc00996 was significantly downregulated in LUAD, and its expression was negatively correlated with T stage, N stage, and pathological stage. An in vitro study suggested that enhanced Linc00996 expression could inhibit cell proliferation, clonal formation, migration, and invasion in LUAD cell lines. Via GSEA and ssGSEA, we observed that Linc00996 might be connected with immune infiltration in LUAD, and Linc00996 might inhibit tumorigenesis and metastasis by regulating antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.Conclusion: Linc00996 is a novel tumor suppressor in LUAD and may suppress the tumorigenesis and metastasis of LUAD via the tumor-related signaling pathway, such as antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.

BackgroundThyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China.MethodsWe carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database.ResultsA total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17–2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38–2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors

Abstract Patients receiving lipid emulsions are at increased risk of contracting catheter-related bloodstream infections (CRBSIs) in the clinic. More than 15% of CRBSIs are polymicrobial. The objective of this study was to explore the effects of lipid emulsions on the formation of Escherichia coli (E. coli)–Candida albicans (C. albicans) mixed-species biofilms (BFs) on polyvinyl chloride (PVC) surfaces and the underlying mechanism. Mixed-species BFs were produced by coculturing E. coli and C. albicans with PVC in various concentrations of lipid emulsions. Crystal violet staining and XTT assays were performed to test the mixed-species BF biomass and the viability of microbes in the BFs. The microstructures of the BFs were observed by an approach that combined confocal laser scanning microscopy, fluorescence in situ hybridization, and scanning electron microscopy. The study found that lipid emulsions could promote the formation of E. coli–C. albicans mixed-species BFs, especially with 10% lipid emulsions. The mechanism by which lipid emulsions promote mixed-species BF formation may involve significant upregulation of the expression of the flhDC, iha, HTA1, and HWP1 genes, which are associated with bacterial motility, adhesion, and BF formation. The results derived from this study necessitate strict aseptic precautions when handling lipid emulsions and avoiding the use of high concentrations of lipid emulsions for as long as possible.

Abstract Objective Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. Materials and methods MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan–Meier survival curves. The publication bias was examined by Egger’s test. Results Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542–1.969, P

Abstract Lung cancer is the leading cause of human cancer mortality due to the lack of early diagnosis technology. The low-dose computed tomography scan (LDCT) is one of the main techniques to screen cancers. However, LDCT still has a risk of radiation exposure and it is not suitable for the general public. In this study, plasma metabolic profiles of lung cancer were performed using a comprehensive metabolomic method with different liquid chromatography methods coupled with a Q-Exactive high-resolution mass spectrometer. Metabolites with different polarities (amino acids, fatty acids, and acylcarnitines) can be detected and identified as differential metabolites of lung cancer in small volumes of plasma. Logistic regression models were further developed to identify cancer stages and types using those significant biomarkers. Using the Variable Importance in Projection (VIP) and the area under the curve (AUC) scores, we have successfully identified the top 5, 10, and 20 metabolites that can be used to differentiate lung cancer stages and types. The discrimination accuracy and AUC score can be as high as 0.829 and 0.869 using the five most significant metabolites. This study demonstrated that using 5 + metabolites (Palmitic acid, Heptadecanoic acid, 4-Oxoproline, Tridecanoic acid, Ornithine, and etc.) has the potential for early lung cancer screening. This finding is useful for transferring the diagnostic technology onto a point-of-care device for lung cancer diagnosis and prognosis.

Abstract Background Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection. Methods We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis. Results All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76–285) minutes and the median blood loss was 50 (range, 20–900) milliliters. The median chest tube duration time was 2 (range, 1–6) days, the median postoperative hospital duration time was 5 (range, 4–10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6–9) and 15(range,12–19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3–6) and 11(range,10–15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death. Conclusions According to our results, it’s effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.

Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.

Surgery is currently the most appropriate treatment for early-stage non-small cell lung cancer (NSCLC). Increasing unilateral or bilateral multiple primary lung cancer being found, segmentectomy has attracted wide attention for its unique advantages in the treatment for such tumors. Ground glass opacity dominant early-stage NSCLC is associated with a good prognosis and can be cured by segmentectomy, however, the treatment of solid-dominant NSCLC remains controversial owing to the invasive nature. With the in-depth study on the lymph node metastasis pathway, radiological characteristics and molecular biology of NSCLC, a large part of solid nodules with certain characteristics can also be cured by segmentectomy. This paper reviews the research status and progress about the indication of segmentectomy.

Backgroud and objective Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese. Methods A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What’s more, all participants were followed up by active or passive follow-up. Results There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P

Abstract Objective It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. Methods Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. Results Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20–2.21) and OS (HR 1.53, 95% CI 1.19–1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45–2.85) and OS (HR 2.26, 95% CI 1.46–3.52) were also poor in the subgroup of patients with the presence of an MP component. Conclusions Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

Background and Objective Yunnan is a country with a high incidence of lung cancer in China and all over the world, and its morbidity and mortality are still rising. With changes in lifestyle and environment, the clinical epidemiological characteristics of lung cancer are converting. However, the trend of clinical characteristics of lung cancer in Yunnan has not been reported in the past 10 years, and we should start further research. The aim of this study was to explore the clinical characteristics and changes of lung cancer in Yunnan from 2005 to 2014, and to provide a theoretical basis for lung cancer prevention and treatment in this region. Methods A retrospective survey was used to extract the cases of lung cancer patients who were treated in our hospital from 2005 to 2014 by simple random sampling. The sociodemographic and clinicopathological characteristics of the patients were extracted by using a unified and standardized questionnaire. And the statistical analysis of the data was performed. Results A total of 1,000 patients with lung cancer were enrolled, with an average age of (58.1±10.1) years, and the ratio of male to female was 3.08/1.00. The proportion of male patients decreased from 75.0% in 2005 to 66.0% in 2014, while female patients increased from 25.0% to 34.0% (P=0.007). The proportion of patients aged ≥60 years increased from 30.0% in 2005 to 39.0% in 2014, and the proportion of patients under 60 years of age decreased, but there was no statistical difference (P=0.532). The proportion of patients with lower levels of education (primary or junior high school) increased from 36.0% to 66.0% (P

Fibroblast activation protein (FAP), a type II transmembrane serine protease, is highly expressed in more than 90% of epithelial tumors and is closely associated with various tumor invasion, metastasis, and prognosis. Using FAP as a target, various FAP inhibitors (FAPIs) have been developed, most of which have nanomolar levels of FAP affinity and high selectivity and are used for positron emission tomography (PET) imaging of different tumors. We have conducted a systematic review of the available data; summarized the biological principles of FAPIs for PET imaging, the synthesis model, and metabolic characteristics of the radiotracer; and compared the respective values of FAPIs and the current mainstream tracer 18F-Fludeoxyglucose (18F-FDG) in the clinical management of tumor and non-tumor lesions. Available research evidence indicates that FAPIs are a molecular imaging tool complementary to 18F-FDG and are expected to be the new molecule of the century with better imaging effects than 18F-FDG in a variety of cancers, including gastrointestinal tumors, liver tumors, breast tumors, and nasopharyngeal carcinoma.

BackgroundInherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links.MethodsTissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics.ResultsOur FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system.ConclusionsThe lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

Biodegradable composites consisting of Poly-(butylene adipate-co-terephthalate) (PBAT), thermoplastic starch, hydrophobically modified nanofibrillated cellulose (HMNC), and green surfactant (sucrose fatty acid ester) were prepared via the melt-mixing and film-blowing process (PBAT-HMNC). The composites were characterized using the Fourier transform infrared spectroscope (FT-IR), scanning electron microscope (SEM), and thermogravimetric analyzer (TGA). The mechanical and barrier properties were systematically studied. The results indicated that PBAT-HMNC composites exhibited excellent mechanical and barrier properties. The tensile strength reached the maximum value (over 13 MPa) when the HMNC content was 0.6% and the thermal decomposition temperature decreased by 1 to 2 °C. The lowest values of the water vapor transmission rate (WVTR) and the oxygen transmission rate (OTR) were obtained from the composite with 0.6 wt% HMNC, prepared via the film-bowing process with the values of 389 g/(m2·day) and 782 cc/(m2·day), which decreased by 51.3% and 42.1%, respectively. The Agaricus mushrooms still had a commodity value after 11 days of preservation using the film with 0.6 wt% HMNC. PBAT-HMNC composites have been proven to be promising nanocomposite materials for packaging.

Objective: Oncogenes have been shown to be drivers of non-small cell lung cancer (NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes (UPGs) that were critical to lung tumorigenesis. Methods: The 696 UPGs were silenced by an siRNA screening in NSCLC cells; the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated. Results: We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs (UBL3, TRIM22, UBE2G2, and MARCH1) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival (OS) of NSCLC patients. Among these genes, UBL3 was the most significant one. UBL3 expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86 (68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC in vitro and in vivo. Conclusions: These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.

Our previous study found that IL33 repressed the growth of pulmonary adenocarcinoma (PA) via regulation of dendritic cells (DCs). However, the molecular mechanism of DCs in PA is still unclear. The present work showed that CYLD−/− mice have a shorter survival rate of PA, and knockout CYLD in DCs also repress the progression of PA in mice. Subsequently, we found that decreased expression and reduced the nuclear translocation of NF-κB signalling was observed in CYLD knockout DCs, and inhibiting NF-κB pathway repressed DCs-induced proliferation and function of CD4+ T cells. These results indicated that CYLD function as a tumour suppresser in PA via regulates the function of DCs through NF-κB signalling pathway. Our findings support that CYLD serves as a potential target for immunotherapy in PA.

Lung adenocarcinoma is one of the leading causes of cancer-related death worldwide. Low expression of Interleukin-33 (IL-33) was reported to be associated with the progression of pulmonary adenocarcinoma. However, the IL-33-mediated immunoregulation in pulmonary adenocarcinoma remains unclear. In this study, we found that IL-33 treatment evidently repressed tumour growth, induced CD4+ T cells infiltration and IL-17 expression in pulmonary adenocarcinoma. Notably, IL-33 treatment increased the number of Dendritic Cells (DCs) in pulmonary adenocarcinoma. More importantly, IL-33 induced maturation and regulated the function of DCs by increasing expression of DCs mature markers (CD40 and CD80, CD86) DCs-function-related gene including antigen presentation genes (HLA-DMA, HLA-DMB and CD74) and cytokines (IL-1β, IL-6 and TNF). Mechanistic studies demonstrated that IL-33 treatment induced DCs maturation by upregulating CYLD expression in DCs. In addition, CYLD played an important role in DCs-induced T cell proliferation and IL-17 secretion. In conclusion, our study demonstrated that IL-33 mediated immunoregulation in pulmonary adenocarcinoma by improving DC-induced T cell proliferation by upregulating CYLD expression.

Abstract Objective Whether segmentectomy can be used to treat radiologically determined pure solid or solid-dominant lung cancer remains controversial owing to the invasive pathologic characteristics of these tumors despite their small size. This meta-analysis compared the oncologic outcomes after lobectomy and segmentectomy regarding relapse-free survival (RFS) and overall survival (OS) in patients with radiologically determined pure solid or solid-dominant clinical stage IA non-small cell lung cancer (NSCLC). Methods A literature search was performed in the MEDLINE, EMBASE, and Cochrane Central databases for information from the date of database inception to March 2019. Studies were selected according to predefined eligibility criteria. The hazard ratio (HR) and associated 95% confidence interval (CI) were extracted or calculated as the outcome measure for data combining. Results Seven eligible studies published between 2014 and 2018 enrolling 1428 patients were included in the current meta-analysis. Compared with lobectomy, segmentectomy had a significant benefit on the RFS of radiologically determined pure solid or solid-dominant clinical stage IA NSCLC patients (combined HR: 1.46; 95% CI, 1.05–2.03; P = 0.024) and there were no significant differences on the OS of these patients (HR: 1.52; 95% CI, 0.95–2.43; P = 0.08). Conclusions Segmentectomy leads to lower survival than lobectomy for clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors. Moreover, applying lobectomy to clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors (≤2 cm) could lead to an even bigger survival advantage. However, there are some limitations in the present study, and more evidence is needed to support the conclusion.