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Abstract Background This study evaluated the prevalence and quantity of lymph nodes at particular stations of the mediastinum in patients with lung cancer. These data are important to radiologists, pathologists, and thoracic surgeons because they can serve as a benchmark when assessing the completeness of lymph node dissection. However, relevant data in the literature are scarce. Methods Data regarding the number of lymph nodes derived from two randomised trials of bilateral mediastinal lymph node dissection, the BML-1 and BML-2 study, were included in this analysis. Detectable nodes at particular stations of the mediastinum and the number of nodes at these stations were analysed. Results The mean number of removed nodes was 28.67 (range, 4–88). Detectable lymph nodes were present at stations 2R, 4R, and 7 in 93%, 98%, and 99% of patients, respectively. Nodes were rarely present at stations 9 L (33%), and 3 (35%). The largest number of nodes was observed at stations 7 and 4R (mean, 5 nodes). Conclusion The number of mediastinal lymph nodes in patients with lung cancer may be greater than that in healthy individuals. Lymph nodes were observed at stations 2R, 4R, and 7 in more than 90% of patients with lung cancer. The largest number of nodes was observed at stations 4R and 7. Detectable nodes were rarely observed at stations 3 and 9 L. Trial registration ISRCTN 86,637,908.

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation, and a plethora of stimuli can induce apoptosis during the progression and treatment of tumors. Moreover, tumor-derived apoptotic extracellular vesicles (apoEVs) are inevitably phagocytosed by live tumor cells, promoting tumor heterogeneity. Understanding the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and recurrence. Herein, we conducted a series of in vivo and in vitro experiments, and we report that tumor-derived apoEVs promoted lung adenocarcinoma (LUAD) metastasis, self-renewal and chemoresistance. Mechanistically, we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor SOX2. In addition, we found that ALDH1A1, which was transported by apoEVs, activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor cells. Furthermore, targeting apoEVs-ALDH1A1 significantly abrogated these effects. Collectively, our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations, and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.

Chemical inhibition is one of the important measures for the prevention and control of coal spontaneous combustion. This paper proposed a quasi-ionic liquid inhibition method based on deep eutectic solvents (DES). First, seven kinds of room temperature deep eutectic solvents were prepared and screened using a heating method. The changes in the functional groups and thermodynamic characteristics of different DES-treated coal samples were analyzed. On this basis, the density functional theory was utilized to analyze the differences in the modification of coal's physicochemical properties by the hydrogen bond strength in the DES, and the inhibition mechanism of deep eutectic solvents and their optimal hydrogen bond strength were deduced. The results showed that after the DES treatment, the hydrogen bond network in coal was disrupted and rearranged. The relative abundance of aliphatic and aromatic hydrocarbons increased by 10%−37%, the content of aliphatic side chains decreased by 9.38%−20.65%, the relative abundance of oxygen-containing functional groups (C=O and C—O) decreased by 22.88%−56.94%, and free low-molecular compound and minerals were leached out. After the DES treatment, the mass loss during the evaporation and desorption stage of coal and the oxygen uptake during the oxygen absorption stage decreased. The heat release during the low temperature oxidation stage and the thermal decomposition stage was reduced by 8.94%−77.51% and 5.40%−26.20%, respectively. The stronger the electronegativity of the hydrogen bond acceptor site in the HBA, the greater the hydrogen bond strength formed between HBA and HBD. The hydrogen bond strength in the DES was positively correlated with the degree of destruction of the hydrogen bond network in coal, and was locally correlated with the oxygen uptake during the oxygen absorption stage, the heat release during low temperature oxidation, and the mineral removal rate. The DES weakened the low-temperature oxidation reactivity of coal by dissolving its active components, and increased the bond dissociation enthalpy of coal by promoting the rearrangement of hydrogen bonds into more thermally stable [OH]4 and OH—N hydrogen bonds. However, the excessive strong hydrogen bond strength would inhibit the removal and dissolution of active side chains. Therefore, the hydrogen bond strength of deep eutectic solvents used to inhibit coal spontaneous combustion should be controlled between 69.45 kJ/mol and 160.00 kJ/mol.

Abstract 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.

Abstract Background Serine protease inhibitors clade B serpins (SERPINBs) are the largest subclass of protease inhibitors, once thought of as a tumor suppressor gene family. However, some SERPINBs exhibit functions unrelated to the inhibition of catalytic activity. Methods The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Set Cancer Analysis (GSCA), and cBioPortal databases were utilized to investigate SERPINBs expression, prognostic correlation, and genomic variation in 33 cancer types. We also conducted a comprehensive transcriptome analysis in multiple lung adenocarcinoma (LUAD) cohorts to reveal the molecular mechanism of SERPINB5 in LUAD. Then, qPCR and immunohistochemistry were used to verify the expression and prognostic value of SERPINB5 in LUAD patients. Furthermore, knockdown and overexpression of SERPINB5 in LUAD cell lines were performed to evaluate cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT). Results The expression of SERPINB5 was upregulated and demethylated in LUAD, and its abnormally high expression was significantly correlated with poor overall survival (OS). In addition, the expression of SERPINB5 was analyzed to determine its prognostic value in LUAD and confirmed that SERPINB5 was an independent predictor of LUAD in TCGA and GEO cohorts and qPCR validation with 106 clinical samples. At last, A knockdown of SERPINB5 in LUAD cells reduced proliferation, migration, and EMT. Proliferation, migration, and invasion are promoted by the overexpression of SERPINB5. Conclusion Therefore, SERPINB5 has shown potential as a prognostic biomarker for LUAD, and it may become a potential therapeutic target for lung adenocarcinoma.

Background The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram’s discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610–0.724]) and 0.697 (95% CIs [0.649–0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

BackgroundPrevious studies had demonstrated that marital status was an independent prognostic factor in multiple cancers. However, the impact of marital status on non-small cell lung cancer (NSCLC) patients was still highly controversial.MethodAll NSCLC patients diagnosed between 2010–2016 were selected from the Surveillance, Epidemiology and End Results (SEER) database. To control the confounding effect of related clinicopathological characteristics, propensity score matching (PSM) was conducted between married and unmarried groups. In addition, independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression. Moreover, nomograms were established based on the clinicopathological characteristics, and the predictive accuracy was assessed by calibration curves. Furthermore, decision curve analysis (DCA) was used to determine the clinical benefits.ResultsIn total, 58,424 NSCLC patients were enrolled according to the selection criteria. After PSM, 20,148 patients were selected into each group for further analysis. The married group consistently demonstrated significantly better OS and CSS compared to unmarried group [OS median survival (95% CI): 25 (24–26) vs. 22 (21–23) months, p

BackgroundLung cancer is one of the cancers with the highest morbidity and mortality. During the last decade, the trends of clinical characteristics, surgical treatments and survival of lung cancer patients in China have remained unclear.MethodsAll lung cancer patients operated on from 2011 to 2020 were identified in a prospectively maintained database of Sun Yat-sen University Cancer Center.ResultsA total of 7,800 lung cancer patients were included in this study. Within the past 10 years, the average age at diagnosis of the patients remained stable, the proportion of asymptomatic, female and nonsmoking patients increased, and the average tumor size decreased from 3.766 to 2.300 cm. In addition, the proportion of early stage and adenocarcinoma increased, while that of squamous cell carcinoma decreased. Among the patients, the proportion of patients having video-assisted thoracic surgery increased. More than 80% of the patients underwent lobectomy and systematic nodal dissection over the 10 years. Additionally, both the average postoperative length of stay and 1-, 3-, and 6-month postoperative mortality decreased. Moreover, the 1-, 3-, and 5-year overall survival (OS) rates of all the operable patients increased from 89.8, 73.9, and 63.8% to 99.6, 90.7, and 80.8%, respectively. The 5-year OS rates of the patients with stage I, II, and III lung cancer were 87.6, 79.9, and 59.9%, respectively, which were higher than those in other published data.ConclusionThere were significant changes in the clinicopathological characteristics, surgical treatments and survival outcomes of the patients with operable lung cancer from 2011 to 2020.

Abstract Background Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. Methods This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. Results Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P

Multi-region sequencing of small cell lung cancers (SCLC) can improve our understanding of the disease. Here the authors analyse 120 multi-region samples from 40 SCLC patients with whole exome sequencing and characterise their mutational burden, evolution, heterogeneity, and potential prognostic biomarkers.

Recent studies have highlighted the combination of activation of host immunogenic cell death (ICD) and tumor-directed cytotoxic strategies. However, overall multiomic analysis of the intrinsic ICD property in lung adenocarcinoma (LUAD) has not been performed. Therefore, the aim of this study was to develop an ICD-based risk scoring system to predict overall survival (OS) and immunotherapeutic efficacy in patients. In our study, both weighted gene co-expression network analysis (WGCNA) and LASSO-Cox analysis were utilized to identify ICDrisk subtypes (ICDrisk). Moreover, we identify genomic alterations and differences in biological processes, analyze the immune microenvironment, and predict the response to immunotherapy in patients with pan-cancer. Importantly, immunogenicity subgroup typing was performed based on the immune score (IS) and microenvironmental tumor neoantigens (meTNAs). Our results demonstrate that ICDrisk subtypes were identified based on 16 genes. Furthermore, high ICDrisk was proved to be a poor prognostic factor in LUAD patients and indicated poor efficacy of immune checkpoint inhibitor (ICI) treatment in patients with pan-cancer. The two ICDrisk subtypes displayed distinct clinicopathologic features, tumor-infiltrating immune cell patterns, and biological processes. The ISlowmeTNAhigh subtype showed low intratumoral heterogeneity (ITH) and immune-activated phenotypes and correlated with better survival than the other subtypes within the high ICDrisk group. This study suggests effective biomarkers for the prediction of OS in LUAD patients and immunotherapeutic response across Pan-cancer and contributes to enhancing our understanding of intrinsic immunogenic tumor cell death.

Background: The tumor microenvironment (TME) is involved in the development and progression of lung carcinomas. A deeper understanding of TME landscape would offer insight into prognostic biomarkers and potential therapeutic targets investigation. To this end, we aimed to identify the TME components of lung cancer and develop a prognostic signature to predict overall survival (OS).Methods: Expression data was retrieved from The Cancer Genome Atlas (TCGA) database and differentially expressed TME-related genes were calculated between tumor and normal tissues. Then nonnegative matrix factorization (NMF) clustering was used to identify two distinct subtypes.Results: Our analysis yielded a gene panel consisting of seven TME-related genes as candidate signature set. With this panel, our model showed that the high-risk group experienced a shorter survival time. This model was further validated by an independent cohort with data from Gene Expression Omnibus (GEO) database (GSE50081 and GSE13213). Additionally, we integrated the clinical factors and risk score to construct a nomogram for predicting prognosis. Our data suggested less immune cells infiltration but more fibroblasts were found in tumor tissues derived from patients at high-risk and those patients exhibited a worse immunotherapy response.Conclusion: The signature set proposed in this work could be an effective model for estimating OS in lung cancer patients. Hopefully analysis of the TME could have the potential to provide novel diagnostic, prognostic and therapeutic opportunities.

Introduction: the investigation on the interactions between ferroptosis and lncRNAs for lung squamous cell carcinoma (LUSC) has been scare, and its impact on tumor immune microenvironment remained unknown. We aim to not only identify a ferroptosis-related lncRNAs signature for LUSC prognosis, but also evaluate its correlation to tumor immune evasion.Methods: RNA sequencing data and survival information were obtained from The Cancer Genome Atlas database. A ferroptosis-related lncRNAs signature (FerRLSig) was developed and validated by univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression and multivariate Cox regression. The tumor immune microenvironment and immune evasion were subsequently evaluated based on the FerRLSig stratification.Results: the FerRLSig consisted of 10 ferroptosis-related lncRNAs and significantly associated with overall survival with satisfactory area under curve (HR = 2.240, 95% CI: 1.845–2.720, p < 0.001, 5-years AUC: 0.756). Based on the FerRLSig stratification, the high-risk group demonstrated not only significantly higher immune infiltration, but also more profound T cell dysfunction and immune evasion, which might ultimately lead to the resistance to current immune checkpoint inhibitors.Conclusion: a robust prognostic FerRLSig for LUSC has been developed and validated, demonstrating a close association not only with tumor immune cell infiltration, but also with T cell dysfunction and immune evasion. Further investigation is warranted to better improve the survival of LUSC patients based on the FerRLSig stratification.

Abstract Background Although the incidence of lymph node (LN) metastasis (LNM) along the left gastric artery is high, its relationship with the prognosis in postoperative patients with esophageal squamous cell carcinoma (ESCC) is rarely reported. This study clarified the prognostic impact of LNM along the left gastric artery in postoperative patients with ESCC. Methods This study assessed data of 1521 patients with ESCC who underwent esophagectomy at the Sun Yat-sen University Cancer Center between March 1992 and March 2012. A chi-squared test and Mann-Whitney U test were used to explore the preliminary correlation between clinical factors and LNM along the left gastric artery. Univariate and multivariate Cox regression analyses were used to assess whether LNM along the left gastric artery was an independent predictor of overall survival. Kaplan–Meier analysis and the log-rank test were used to present a classifying effect based on LN status. Results LNM was observed in 598 patients (39.3%) and was found along the branches of the left gastric artery in 256 patients (16.8%). The patients were classified into two groups based on the presence of LNM along the left gastric artery. Patients without LNM along the left gastric artery had better cancer-specific survival than those with positive LNs (P

Background and objective Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). Methods This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. Results This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. Conclusion Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

ObjectiveDue to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce.MethodsPatients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan–Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors.ResultsA total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P < 0.001), had smaller tumor size (P = 0.010), and less lymph nodes dissection (P < 0.001). The 5-year CSS and OS rates were 56.5 and 42.9% for SLR, and 67.8 and 55.7% for lobectomy, respectively (P = 0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between the SLR group and lobectomy group in CSS (P = 0.135) and OS (P = 0.285); and the PSM also supported these results. In addition, the age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS.ConclusionsAlthough SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should still be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.

BackgroundGenomic instability is one of the representative features of cancer evolution. Recent research has revealed that long noncoding RNAs (lncRNAs) play a critical role in maintaining genomic instability. Our work proposed a gene signature (GILncSig) based on genomic instability-derived lncRNAs to probe the possibility of lncRNA signatures as an index of genomic instability, providing a potential new approach to identify genomic instability-related cancer biomarkers.MethodsLung adenocarcinoma (LUAD) gene expression data from an RNA-seq FPKM dataset, somatic mutation information and relevant clinical materials were downloaded from The Cancer Genome Atlas (TCGA). A prognostic model consisting of genomic instability-related lncRNAs was constructed, termed GILncSig, to calculate the risk score. We validated GILncSig using data from the Gene Expression Omnibus (GEO) database. In this study, we used R software for data analysis.ResultsThrough univariate and multivariate Cox regression analyses, five genomic instability-associated lncRNAs (LINC01671, LINC01116, LINC01214, lncRNA PTCSC3, and LINC02555) were identified. We constructed a lncRNA signature (GILncSig) related to genomic instability. LUAD patients were classified into two risk groups by GILncSig. The results showed that the survival rate of LUAD patients in the low-risk group was higher than that of those in the high-risk group. Then, we verified GILncSig in the GEO database. GILncSig was associated with the genomic mutation rate of LUAD. We also used GILncSig to divide TP53 mutant-type patients and TP53 wild-type patients into two groups and performed prognostic analysis. The results suggested that compared with TP53 mutation status, GILncSig may have better prognostic significance.ConclusionsBy combining the lncRNA expression profiles associated with somatic mutations and the corresponding clinical characteristics of LUAD, a lncRNA signature (GILncSig) related to genomic instability was established.

The molecular connection between nitrogen utilization efficiency (NUE) and biomass production is unclear. Here, the authors show that differences in NUE and cellulose biogenesis between rice indica and japonica subspecies can be explained by variation at the MYB61 locus, which is regulated by the NUE regulator GRF4.

Refolding of human interleukin 17A (IL-17A) has been reported; however, the key refolding protocol was not robust enough to deliver consistent results and to be easily scaled up for crystallization. Here we report an optimized refolding method for IL-17A. Although co-crystal structures of IL-17A with ligands have been obtained with a high-affinity peptide and an anti-IL-17A Fab as stabilizers, neither the production yield nor the characterization of the IL-17A/Fab complex was reported. To facilitate co-crystallization of IL-17A with small-molecule compounds derived from our DNA encoded library, we also describe the method for yield enhancement of anti-IL-17A Fab production and characterize the IL-17A/Fab complex for the first time, providing an essential prerequisite for structure-based drug discovery targeting IL-17A.

Background and Objective It is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. The purpose of this study is to explore the feasibility and necessity of the localization of pulmonary nodules by injecting indocyanine green (ICG) under the guidance of magnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope. Methods Between December 2018 and August 2019, sixteen consecutive patients with 30 peripheral lung lesions in our hospital received fluorescent thoracoscopic pulmonary nodule resection. Electromagnetic navigation bronchoscope (ENB) was performed before surgery to guide ICG to the target lesion. Results All patients underwent magnetic navigation-guided pulmonary nodule localization, and surgical resection was performed immediately after localization was completed. The average size of the nodules was (11.12±3.65) mm. The average navigation time was (12.06±2.74) minutes, and the average interval between dye labeling and lung resection was (25.00±5.29) minutes. All lesions were completely resected, the localization success rate was 100.00%, no bleeding and other complications occurred after the localization, the postoperative pathological results confirmed the accuracy of the staining. Conclusion Indocyanine green injection under the guidance of magnetic navigation bronchoscope is an effective way to locate pulmonary nodules, which can locate small and untouchable lesions in the lung. This method can help surgeons identify lesions more quickly and accurately. It is practical and worthy of promotion.

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC.Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1–2, 3–8, and ≥9 lymph nodes) and 3 groups (0, 1–3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis.Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438–0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476–0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups.Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

The rare lung cancer subtype pulmonary lymphoepithelioma-like carcinoma is linked to Epstein-Barr virus infection. Here, the authors provide a mutational landscape for this cancer, showing a low burden of somatic mutations and high prevalence of copy number variations.

Abstract High-level tissue tumor mutational burden (tTMB) or blood TMB (bTMB) are associated with better response of immunotherapy in non-small cell lung cancer (NSCLC) patients. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified. We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and evaluated single-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. TMB of > 9 mutations/Mb was classified as high. Besides, we used tTMB fold-change to evaluate the influence of the enrolled region number on tTMB. We found both of single-region tTMB and bTMB showed strong correlations with multi-region tTMB, while the former correlated better (Pearson r = 0.94, P = 2E-84; Pearson r = 0.47, P = 0.0067). It showed extremely high specificity (100%) but low sensitivity (43%) when using bTMB to define TMB-high patients, while most false-negative predictions were in early-stage patients. Compared to single region, we found significantly enhanced tTMB fold-change if taking multi-regions for consideration. However, it showed insignificant tTMB fold-change increase if the included regions’ number more than three. Moreover, ITH-high patients had significantly higher tTMB fold-change compared with ITH-low patients (2.32 vs. 1.02, P = 8.879e-05). The conversion rate of tTMB level (tTMB-low to tTMB-high) was numerically higher in ITH-high group than that in ITH-low group (16.67% vs. 3.84%). In summary, single-region tTMB has stronger correlation with multi-region tTMB compared with bTMB. ITH has an impact on tTMB, especially in high-level ITH patients.

Abstract Understanding of intratumor heterogeneity (ITH) among different non-small cell lung cancer (NSCLC) subtypes is necessary. Whether circulating tumor DNA (ctDNA) profile could represent these ITH is still an open question. We performed 181 multi-region tumor tissues sequencing and matched ctDNA sequencing from 32 operative NSCLC to compare ITH among different NSCLC subtypes, including EGFR-mutant lung adenocarcinoma (LUAD), KRAS-mutant LUAD, EGFR&KRAS-wild-type LUAD, and lung squamous cell carcinoma (LUSC), and examine potential value of ctDNA for ITH analysis. ITH is evaluated by ITH index (ITHi). If the somatic genetic alteration is shared by all the tissue regions, it is defined as trunk mutation. Otherwise, it is called branch mutation. The ITHi will be higher, if the tumor has less trunk mutations. We found EGFR-mutant LUAD showed significantly higher ITHi than KRAS-mutant LUAD/wild-type LUAD (P = 0.03) and numerically higher ITH than LUSC. For trunk mutations, driver mutations were identified at a higher proportion than passenger mutations (60% vs. 40%, P = 0.0023) in overall, especially in EGFR-mutant LUAD (86% vs. 14%, P = 0.0004), while it was opposite in KRAS-mutant LUAD (40% vs. 60%, P = 0.18). For branch mutations, the proportions of driver mutations and passenger mutations were similar for each NSCLC subtype. ctDNA analysis showed unsatisfactory detections of tumor-derived trunk and branch mutations (43% vs. 23%, P = 4.53e-6) among all NSCLC subtypes. In summary, EGFR-mutant LUAD has the highest ITH than other NSCLC subtypes, offering further understanding of tumorigenesis mechanisms among different NSCLC subtypes. Besides, ctDNA maybe not an appropriate method to reflect ITH.

Coal spontaneous combustion (CSC) is a disaster that seriously threatens safe production in coal mines. Revealing the mechanism of CSC can provide a theoretical basis for its prevention and control. Compared with experimental research is limited by the complexity of coal molecular structure, the quantum chemical calculation method can simplify the complex molecular structure and realize the exploration of the mechanism of CSC from the micro level. In this study, toluene and phenylacetaldehyde were used as model compounds, and the quantum chemical calculation method was adopted. The reaction processes of the methyl and aldehyde groups with oxygen were investigated with the aid of the Gaussian 09 software, using the B3LYP functional and the 6-311 + G(d,p) basis set and including the D3 dispersion correction. On this basis, the generation mechanisms of CO and CO2, two important indicator gases in the process of CSC, were explored. The calculation results show that the Gibbs free energy changes and enthalpy changes in the two reaction systems are both of negative values. Accordingly, it is judged that the reactions belong to spontaneous exothermic reactions. In the reaction processes, the activation energy of CO is less than that of CO2, indicating that CO is formed more easily in the above-two reaction processes. In addition, the variations in concentrations of important oxidation products (CO and CO2) and main active functional groups (such as methyl, carboxyl and carbonyl) with temperature were revealed through a low-temperature oxidation experiment. The experimental results verify the accuracy of the above quantum chemical reaction path. Moreover, it is also found that the generation mechanisms of CO and CO2 in coal samples with different metamorphic degrees are different. To be specific, for low-rank coal (HYH), CO and CO2 mainly come from the oxidation of alkyl side chains; for high-rank coal (CQ), CO is produced by the oxidation of alkyl side chains, and CO2 is attributed to the inherent oxygen-containing structure.

BackgroundGrade prognostic assessment (GPA) is widely used to evaluate the prognosis of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This study aimed to investigate whether lymph node status (LNS) could be included as one of the GPA variables for NSCLC with BMs.MethodsOverall, 586 patients with NSCLC and BMs were retrospectively analyzed. Overall survival stratified by LNS was analyzed using the Kaplan-Meier method. Multivariate analysis was also performed to identify independent prognostic factors using the Cox proportional hazards progression model. In the updated GPA index, prognostic factors and criteria of GPA score were weighted by effect magnitude relative risk (RR) and statistical significance.ResultsIn NSCLC patients with BMs, those with lymph node involvement had worse overall survival (mOS, 13.4 months vs. 25.9 months, P

Background: We previously identified a 12-microRNA (miRNA) panel (miRNA-17, miRNA-146a, miRNA-200b, miRNA-182, miRNA-155, miRNA-221, miRNA-205, miRNA-126, miRNA-7, miRNA-21, miRNA-145, and miRNA-210) that aided in the early diagnosis of non-small cell lung cancer (NSCLC). We validated the diagnostic value of this miRNA panel and compared it with that of traditional tumor markers and radiological diagnosis. We constructed a nomogram based on the miRNA panel's results to predict the risk of NSCLC.Methods: Eighty-two participants with pulmonary nodules on a CT scan and who underwent a pathological examination and surgical treatment were enrolled in our study. Patients were randomly divided into a training group or a validation group. The miRNA concentrations were quantified by RT-PCR and log-transformed for analysis. The cutoff value was determined in the training group and then applied in the validation group. A comparison between the miRNAs and traditional tumor markers [CEA, NSE, and cytokeratin 19 fragment 21-1 (Cyfra21-1)] and radiological diagnosis was performed. A nomogram based on the miRNA panel's results to predict the risk of NSCLC was constructed.Results: The expression level of these 12 miRNAs was significantly higher in NSCLC patients than in benign patients. In the validation group, the specificity and positive predictive value were 96.4 and 95.8%, respectively, which were significantly higher than those using traditional tumor markers or radiological diagnosis. The sensitivity was 42.6%, which was also higher than that using tumor markers. Moreover, the sensitivity increased to 63.6% when the nodule diameters were larger than 2 cm. The miRNAs and seven clinical factors were integrated into the nomogram, and the calibration curves showed optimal agreement between the predicted and actual probabilities.Conclusions: Our miRNA panel has clinical value for the early detection of NSCLC. A nomogram was constructed and internally validated, and the results indicate that it can assist clinicians in making treatment recommendations in the clinic.

Introduction: A certain number of small cell lung cancer (SCLC) patients become long-term survivors after treatment, and they are at high risk to develop a second primary malignancy, including non-small cell lung cancer. However, the optimal management of early-stage second primary non-small cell lung cancer (SPLC) after SCLC remains unknown. This study aims to evaluate the survival benefits of surgery in these patients.Methods: Patients with early-stage SPLC after SCLC were identified from the Surveillance, Epidemiology, and End Results database. Patients were balanced with propensity score matching (PSM). Overall survival (OS) and lung cancer-specific survival (CSS) were compared between non-surgery group and surgery group with the Kaplan–Meier method and Cox multivariate regressions.Results: A total of 228 patients with early-stage SPLC after SCLC were identified. Surgery was associated with significantly improved OS and CSS in the multivariate Cox regression analysis (OS, 5-year survival: 41.2 vs. 11.6%, HR: 0.42, 95% CI: 0.31–0.59, P < 0.01; CSS, 5-year survival: 46.8 vs. 24.3%, HR: 0.53, 95% CI: 0.37–0.75, P < 0.01). However, no statistically significant survival difference was found between sublobar resection and lobectomy (OS, 5-year survival: 41.0 vs. 45.3%, P = 0.73; CSS, 5-year survival: 43.5 vs. 54.1%, P = 0.49). After 1:1 PSM, 162 patients were selected for further analysis, and surgery continued to demonstrate superior survival (OS, 5-year survival: 44.2 vs. 7.2%, HR: 0.48, 95% CI: 0.33–0.70, P < 0.01; CSS, 5-year survival: 48.0 vs. 20.6%, HR: 0.44, 95% CI: 0.42–0.97, P = 0.03).Conclusion: The resection of early-stage SPLC after SCLC led to significantly improved OS and CSS and therefore should be considered whenever possible. Nevertheless, further randomized controlled trials are warranted to investigate the safety and effect of surgery in these patients.

Unilateral cross-incompatibility between certain varieties of maize prevents cross-fertilization and can facilitate hybrid breeding. Here the authors show that a PECTIN METHYLESTERASE gene is able to overcome this reproductive barrier and confer fertility when expressed in pollen of the male parent.

Abstract Background The antitumour efficacy of tyrosine kinase inhibitors (TKIs) in lung cancer patients with compound epidermal growth factor receptor (EGFR) mutations has not been resolved. Our study summarizes a single institutional experience of first-generation TKI therapy for lung cancers with compound EGFR mutations. Methods A total of 106 consecutive patients with tumours bearing compound EGFR mutations were identified between January 2012 and May 2016; all patients received first-generation TKI therapy. Deletions in exon 19 and the L858R point mutation in exon 21 were considered common mutations; T790M was considered separately because of its association with TKIs resistances. Any other mutation was defined as a rare mutation. Patients were divided as follows: double common mutations (group A); common plus T790M mutations (group B); common plus rare mutations (group C); double rare mutations (group D); and rare plus T790M mutations (group E). A separate group of 115 consecutive patients with a single common mutation was created for comparative analysis (group F). Results The frequency of patients with compound EGFR was 2.9% (114/3925) and their response rate to first-generation TKIs was 50.9%, which was not significantly different from group F (67.0%, P = 0.088). The progression-free survival (PFS) of the 106 patients receiving TKI therapy was worse than that of group F (median, 9.1 vs. 13.0 months, respectively; P

Background and objective As computed tomography (CT) screening for lung cancer becomes more common in China, so too does detection of pulmonary ground-glass nodules (GGNs). Although anumber of national or international guidelines about pulmonary GGNs have been published,most of these guidelines are produced by respiratory, oncology or radiology physicians, who might not fully understand the progress of modern minimal invasive thoracic surgery, and these current guidelines may overlook or underestimate the value of thoracic surgery in the management of pulmonary GGNs. In addition, the management for pre-invasive adenocarcinoma is still controversial. Based onthe available literature and experience from Shanghai Pulmonary Hospital, we composed this consensus about diagnosis and treatment of pulmonary GGNs. For lesions which are considered as adenocarcinoma in situ, chest thin layer CT scan follow-up is recommended and resection can only be adopt in some specific cases and excision should not exceed single segment resection. For lesions which are considered as minimal invasive adenocarcinoma, limited pulmonary resection or lobectomy is recommended. For lesions which are considered as early stage invasive adenocarcinoma, pulmonary resection is recommend and optimal surgical methods depend on whether ground glass component exist, location, volume and number of the lesions and physical status of patients. Principle of management of multiple pulmonary nodules is that primary lesions should be handled with priority, with secondary lesions taking into account.

Lymph node metastasis is an important route of metastasis of lung cancer. Lymphadenectomy has become the standard surgical procedure for lung cancer. The way of intraoperative lymph node assessment also affects the prognosis and treatment strategy of lung cancer. In clinical practice, the way of intraoperative lymph node assessment ranges from selected lymph node biopsy to extended lymph node dissection. The advantages and disadvantages of different lymph node assessment are still controversial. In this article, the argument and consensus of lymphadenectomy on lung cancer operation are summarized.

The plant cell wall is a complicated network that is mainly constituted of polysaccharides, such as cellulose, hemicellulose and pectin. Many noncellulosic polysaccharides are further acetylated, which confers these polymers flexible physicochemical properties. Due to the significance of cell wall in plant growth and development, the analytic platform has been the focus for a long time. Here, we use internodes/culms, an important organ to provide mechanical support for rice plants, as an experimental sample to explore the method for cell wall composition analysis. The method includes preparation of cell wall residues, sequential extraction of polysaccharides, and measurement of cellulose. The procedure for acetate examination is also described. This method is applicable to determine the composition of individual cell wall polymers and the modifier acetates, and is suitable to identify cell wall relevant mutants based on the advantages in high throughput, precision and repeatability.

Objective: The purpose of this study was to evaluate the diagnostic efficiency of combining plasma microRNAs (miRNAs) and computed tomography (CT) features in the diagnosis of pulmonary nodules.Methods: Ninety-two pulmonary nodule patients who had undergone surgery were enrolled in our study from July 2016 to March 2018 at the Sun Yat-sen University Cancer Center. A prediction model was established by combining 3 miRNAs (miRNA-146a, -200b, and -7) and CT features to identify the pulmonary nodules of these patients. We evaluated the diagnostic performance of this prediction model for pulmonary nodules using the Receiver Operating Characteristic (ROC) curve.Results: The expression levels of miRNA-146a, -200b, and -7 in early-stage non-small cell lung cancer (NSCLC) patients are significantly higher than those in benign nodule patients. We used these three miRNAs and CT features (pleural indentation and speculation) to establish a prediction model for early-stage NSCLC, with a sensitivity and specificity of 92.9%, 83.3% in the training set, respectively. For the validation process, with the sensitivity of 71.8% and the specificity of 69.2%. For ROC curve analyses, area under the curve (AUC) for tumor identification in the training stage and validation stage were 0.929 and 0.781, respectively.Conclusion: Plasma miRNA-146a, miRNA-200b, and miRNA-7 may be potential biomarkers for the early diagnosis of lung cancer. Our prediction model can help to identify the nature of pulmonary nodules with a relatively high diagnostic efficiency.

Background: To investigate the prognostic impact of different types of lymphadenectomy with different extents of tumor resection on the outcomes of stage I non-small-cell lung cancer (NSCLC).Methods: Patients were classified into lobectomy and sublobectomy groups, and then each group was subdivided according to the types of lymphadenectomy. The end points of the study were overall survival (OS) and disease-free survival (DFS). Propensity score matched (PSM) comparative analysis and univariate and multivariate Cox regression analyses were performed.Result: A total of 1,336 patients were included in the current study. Lobectomy was associated with better OS and DFS. In the lobectomy group, lobectomy with bilateral mediastinal lymphadenectomy (BML) was associated with better OS than lobectomy with systematic nodal dissection (SND) or lobe-specific systematic node dissection (L-SND). Lobectomy with SND or L-SND was associated with better OS than lobectomy with systematic nodal sampling (SNS) or selected lymph node biopsy (SLNB). Additionally, lobectomy with BML or SND was associated with better DFS than lobectomy with L-SND or SNS or SLNB. After PSM, compared with lobectomy with SNS or SLNB, lobectomy with SND resulted in more favorable OS and DFS. There was no survival difference between different types of lymphadenectomy for patients who underwent sublobectomy. A multivariable analysis revealed independent associations of lobectomy with BML or SND with better OS and DFS compared with those of lobectomy with SNS or SLNB.Conclusion: This study reveals an association of lobectomy with more systematic and complete lymph node dissection, such as BML or SND, with better prognosis in stage I NSCLC patients.

This paper selects two typical compounds containing organic sulfur as model compounds. Then, by analyzing the chromatograms of gaseous low-temp oxidation products and GC/MS of the extractable matter of the oxidation residue, we summarizing the mechanism of low-temp sulfur model compound oxidation. The results show that between 30 °C to 80 °C, the interaction between diphenyl sulfide and oxygen is mainly one of physical adsorption. After 80 °C, chemical adsorption and chemical reactions begin. The main reaction mechanism in the low-temp oxidation of the model compound diphenyl sulfide is diphenyl sulfide generates diphenyl sulfoxide, and then this sulfoxide is further oxidized to diphenyl sulphone. A small amount of free radicals is generated in the process. The model compound cysteine behaves differently from diphenyl sulfide. The main reaction low-temp oxidation mechanism involves the thiol being oxidized into a disulphide and finally evolving to sulfonic acid, along with SO2 being released at 130 °C and also a small amount of free radicals. We also conducted an experiment on coal from Xingcheng using X-ray photoelectron spectroscopy (XPS). The results show that the major forms of organic sulfur in the original coal sample are thiophene and sulfone. Therefore, it can be inferred that there is none or little mercaptan and thiophenol in the original coal. After low-temp oxidation, the form of organic sulfur changes. The sulfide sulfur is oxidized to the sulfoxide, and then the sulfoxide is further oxidized to a sulfone, and these steps can be easily carried out under experimental conditions. What’s more, the results illustrate that oxidation promotes sulfur element enrichment on the surface of coal.

Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity.

The structure and distribution of organic sulfur in coals of different rank and different sulfur content were studied by combining mild organic solvent extraction with XPS technology. The XPS results have shown that the distribution of organic sulfur in coal is related to the degree of metamorphism of coal. Namely, thiophenic sulfur content is reduced with decreasing metamorphic degree; sulfonic acid content rises with decreasing metamorphic degree; the contents of sulfate sulfur, sulfoxide and sulfone are rarely related with metamorphic degree. The solvent extraction and GC/MS test results have also shown that the composition and structure of free and soluble organic sulfur small molecules in coal is closely related to the metamorphic degree of coal. The free organic sulfur small molecules in coal of low metamorphic degree are mainly composed of aliphatic sulfides, while those in coal of medium and high metamorphic degree are mainly composed of thiophenes. Besides, the degree of aromatization of organic sulfur small molecules rises with increasing degree of coalification.