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Background Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the leading major histological phenotypes of all non-small cell lung cancer (NSCLC). In this study, the candidate genes and the potential tumorigenesis distinguishing between LUAD and LUSC were analyzed. Methods The present study investigated two microarray datasets (GSE28571 and GSE10245) downloaded from the Gene Expression Omnibus (GEO) database. A protein-protein interaction (PPI) network was applied to screen out the candidate genes. In addition, differently expressed genes (DEGs) between lung adenocarcinoma and lung squamous cell carcinoma of the two datasets were functionally analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. R 4.0.2 was used to perform Kaplan-Meier analysis of DSG3 (desmoglein 3) and KRT14 (keratin 14) by analyzing the expression and clinical data from The Cancer Genome Atlas (TCGA) database. Results The results revealed that 47 DEGs of the two datasets were ascertained in our study. It was found that the DEGs were mainly involved in pathways related to p63 transcription factor network and validated transcriptional factor targeting TAp63, etc. Based on the analysis, we finally identified DSG3 and KRT14 as potential biomarkers for distinguishing between LUAD and LUSC. These results suggested that DSG3 and KRT14 could have the potential to play an important role in NSCLC patients, as diagnostic markers. At the same time, DSG3 or KRT14 indicated a worse prognosis in LUSC patients, which were associated with pathways relevant to the TRAIL signaling pathway and TNF receptor signaling pathway according to bioinformatic analysis. Conclusion The DSG3 and KRT14 have the potential to be used as diagnostic markers, which presented here may facilitate improvements in distinguishing between LUAD and LUSC in advanced NSCLC patients.

Gefitinib, the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has become the standard of care for the first-line of therapy for advanced non-small cell lung cancer (NSCLC) with common EGFR mutation. However, the efficacy of preoperative gefitinib therapy in patients with common EGFR mutations remains poorly defined. We describe a NSCLC patient with bilateral synchronous lesions who had a significantly positive response to gefitinib before radical surgical resection. At the time of initial diagnosis, we were unable to confirm whether the two lesions were metastatic or synchronous primary lesions. Accordingly, we performed CT-guided percutaneous left lung biopsy resulting in a diagnosis of lung adenocarcinoma with exon 21 L858R point mutation of EGFR, This diagnosis was followed by preoperative gefitinib therapy for 8 weeks leading to a significant reduction in the lesion in the left lower lobe. Then the left lower lobectomy and mediastinal lymphadenectomy were performed. In addition, 3 months following resection of the left lower lobe tumor the patient underwent a right lower lobe wedge resection. This report indicates that NSCLC patient harboring common EGFR mutation accepting the first-generation EGFR-TKI gefitinib as a neoadjuvant targeted therapy option is safe, feasible, and well-tolerated.

BACKGROUND Affected by the COVID-19, a great many patients were quarantined and could not go to the hospital, which made the outpatient follow-up unable to be carried out normally. OBJECTIVE Our study aimed to assess the feasibility of a postoperative follow-up cloud platform based on a standardized discourse form among postoperative patients with lung cancer in COVID-19 pandemic. METHODS The postoperative follow-up cloud platform was established by designing a standardized discourse form, and constructing a follow-up database and a health education center. The follow-up team was comprised of fixed and experienced full-time doctors. A total of 184 and 178 patients as the intervention and control group, who were followed up by the cloud platform and outpatient department. At the end of the follow-up period, our center carried out the satisfaction with follow-up and SF-36 health questionnaire survey. RESULTS There was no statistically significant difference in the baseline characteristics of the patients between the two groups. At the end of the follow-up period, satisfaction with follow-up in the intervention group was better than that in the control group (96.74%, 178/184 vs 87.08%, 155/178; P＜0.001). The intervention group had the similar results compared with the control group in SF-36 scales (Average, 64.79±13.59 vs 63.07±15.00; P=0.256). CONCLUSIONS The postoperative follow-up cloud platform based on a standardized discourse form can break the limitations of time and space, improve medical service and doctor-patient communication, and promote scientific research, which is feasible in COVID-19 pandemic.

Oral and esophageal squamous cell carcinomas (SCCs) are associated with high mortality, yet the molecular mechanisms underlying these malignancies are largely unclear. We show that DNA hypermethylation of otubain 2 (OTUB2), a previously recognized oncogene, drives tongue and esophageal SCC initiation and drug resistance. Mechanistically, OTUB2 promotes the deubiquitination and phosphorylation of signal transducer and activator of transcription 1 (STAT1) and subsequently regulates the transcription of calmodulin-like protein 3 (CALML3). Activation of CALML3-mediated mitochondrial calcium signaling promotes oxidative phosphorylation (OXPHOS) and the synthesis of phosphatidylserine (PS). In mouse models, orally administered soybean-derived PS inhibits SCC initiation in cells with low OTUB2 expression and increases their sensitivity to chemotherapy. Our study indicates that the OTUB2/STAT1/CALML3/PS axis plays tumor-suppressive roles and shows the potential of PS administration as a strategy for the treatment and prevention of tongue and esophageal SCCs.

Background Circular RNA has been revealed as a potential biomarker in multiple malignancies. However, few studies have focused on its potential to be prognostic markers in lung squamous cell carcinoma (LSCC). In this work, we aimed to build a prognostic model of resected LSCC based on circular RNA pyruvate dehydrogenase kinase 1 (circPDK1) and other clinicopathological factors. Methods circPDK1 was identified via next-generation sequencing. Three hundred two cases of LSCC tissue and their adjacent normal lung tissues were obtained from multiple medical centers and divided into study cohort (n=232) and validation cohort (n=70). The expression of circPDK1 was detected for analyzing its potential prognostic value for recurrence-free survival (RFS) and overall survival (OS) in LSCC. Finally, combined with circPDK1, T staging, lymph nodes (LN) metastasis status, age, and serum squamous cell Carcinoma Antigen (SCCAg), we built a prognostic model by nomograms method and confirmed it in the validation cohort. Results CircPDK1 was identified to be overexpressed (P

Lung cancer leads to the most cancer-related death in the world. It was shown from the increasing evidences that long non-coding RNAs (lncRNAs) are emerging as molecules for diagnosis, prognosis and even therapy of lung cancer and other malignancies. The biological functions or involved signaling pathways of lncRNAs are always found to be inconsistent among different types of malignancies. However, no available literature has systemically summarized differences in the functions and underlying molecular mechanisms of lncRNAs between lung cancer and other cancers. In this review, the biological functions and molecular mechanisms of lncRNAs in lung cancer were introduced. Furthermore, their functional differences between lung cancer and other malignancies were discussed. Finally, their potential clinical applications in future lung cancer therapy were focused on.

Background Segmentectomy is increasingly used to resect lung nodules. Robotic-assisted thoracic surgery (RATS) is considered a safe and practical method for segmentectomy. Few studies have compared robotic surgery and video-assisted thoracic surgery (VATS) for lung segmentectomy. Method We retrospectively examined 215 consecutive patients who underwent typical (88 patients) or atypical (128 patients) segmentectomy by either robotic surgery or VATS. The postoperative characteristics including operation time, blood loss, pneumonia, tumor size, lymph nodes harvested, chest tube duration, prolonged air leak, atrial fibrillation, and postoperative hospital stay were recorded. Results A total of 88 patients underwent typical segmentectomy, while 127 patients underwent atypical segmentectomy. A greater number of lymph nodes were resected via RATS than by VATS (13.24 ± 4.84 vs. 11.71 ± 3.89; P = 0.018). The operation time for typical segmentectomy was shorter than that for atypical segmentectomy (115.69 ± 22.32 vs. 131.68 ± 22.52; P = 0). No significant differences were found between RATS and VATS in terms of chest drainage duration and postoperative hospital stay. The incidence of postoperative complications including prolonged air leak and atrial fibrillation was not significantly different between typical segmentectomy and atypical segmentectomy. Conclusion Atypical segmentectomy is more complicated than typical segmentectomy, which may lead to increases in complications and operation time. Robotic surgery was safe and practical for segmentectomy compared to VATS and more lymph nodes could be dissected by RATS without increasing the risk of postoperative complications.

Background This study was conducted to investigate the effect of P14 promoter aberrant methylation on the biological function of human lung adenocarcinoma cells. Methods We used nested methylation‐specific PCR (NMSP) to detect the methylation status of the p14ARF promoter region in SPCA1 and BEAS2B cell lines. The experimental groups were treated with 5‐aza‐2′‐deoxycytidine (5‐Aza). Quantitative real‐time PCR, Western blot, flow cytometry, and Cell Counting Kit 8 were used to detect the expression of p14ARF messenger RNA and protein in each group, apoptosis, and cell proliferation inhibition, respectively. Results NMSP detected that the p14 promoter region of SPCA1 cells has abnormal methylation status. After treatment with 5‐Aza, the expression of p14ARF messenger RNA and protein in SPCA1 cells (P 0.05). Conclusion Abnormal methylation of the p14ARF promoter region plays an important role in the development of lung cancer cells. Our results suggest the use of P14 promoter aberrant methylation as a therapeutic target for drug research or to improve the sensitivity of other drugs.

Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR‐638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT‐PCR results demonstrating miR‐638 was obviously up‐regulated in calcific aortic valves compared with non‐calcific valves. We also proved that miR‐638 was significantly up‐regulated during hAVICs osteogenic differentiation. Overexpression of miR‐638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down‐regulation of miR‐638 enhance the process. Target prediction analysis and dual‐luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR‐638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up‐regulation miR‐638. Our data indicated that miR‐638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR‐638 may be a potential therapeutic target for CAVD.

Objectives Tumor spread through air spaces (STAS) was recently reported as a novel risk factor for the prognosis of patients with resected lung adenocarcinoma that indicates invasive tumor behavior. The purpose of this study was to build a prognostic model consisting of STAS and other pathologic features including visceral pleural invasion (VPI), vascular invasion (VI) and histological subtype (HS) in lung invasive adenocarcinoma. Materials and methods A total of 289 patients with resected lung invasive adenocarcinomas ≤4 cm were analyzed retrospectively to evaluate the potential prognostic value of STAS, VPI, VI and HS for recurrence-free survival (RFS) and overall survival (OS). Results STAS was observed in 143 patients (49.5%). Univariate and multivariate analysis showed that STAS, VPI, VI and HS were significant prognostic factors for poorer RFS and OS. Thus, a prognostic model including STAS, VPI, VI and HS was built using the results of the multivariate analysis. Nomograms were developed to predict the 5-year RFS and OS. The concordance index (C-index) of the prognostic model was 0.8122 for predicting 5-year RFS and 0.8539 for predicting 5-year OS in the internal validation. Moreover, the calibration curves for the 5-year RFS and OS showed that the nomograms were calibrated well. In addition, a similar predicted capability of the prognostic model was observed in the validation cohort. Conclusion STAS, VPI, VI and HS were significant prognostic factors for poorer RFS and OS. The prognostic model including STAS, VPI, VI and HS could effectively predict prognosis.

The treatment of lung cancer is one of the major challenges in the field of oncology. According to statistics from the National Cancer Center of China in 2015, lung cancer has the highest incidence and mortality, with 733,300 new cases and 610,200 deaths across the country (1). About 85% of lung cancers are non-small cell lung cancer (NSCLC), of which 30% to 40% are considered resectable tumors, including most stage I-II and a small portion of stage IIIA tumors (2). Very early-stage NSCLC (IA) can be cured by surgery. However, more than 50% of NSCLC patients who undergo surgical treatment will relapse or metastasize within 5 years. Even if there is no lymph node metastasis and the primary

BACKGROUND: We sought to determine the perioperative safety and feasibility outcomes of stage IIIA (N2) non-small cell lung cancer (NSCLC) following neoadjuvant immunotherapy or neoadjuvant chemotherapy. METHODS: The clinical details of patients who attended the Affiliated Hospital of Qingdao University between January 2019 and December 2020 were retrospectively evaluated. Eligible patients had pathologically proven stage IIIA (N2) NSCLC and were randomly prescribed neoadjuvant therapy. Those in the neoadjuvant immunotherapy group received two cycles of nivolumab (3 mg/kg) and those in the control group received neoadjuvant chemotherapy (1,000 mg/m(2) gemcitabine and 80 mg/m(2) cisplatin). All patients were scheduled to undergo surgery. The primary endpoint was the risk of major complications within 30 days of surgery and the secondary endpoints were interval to surgery and 30-day mortality. RESULTS: A total of 107 eligible patients were evaluated of whom 25 were allocated to the neoadjuvant immunotherapy group and 82 to the neoadjuvant chemotherapy group. The median interval to surgery was similar in the two groups at 29.2 days [95% confidence interval (CI), 27.1 to 31.4 days] in the immunotherapy group and 28.7 days (95% CI, 27.6 to 29.8 days) in the chemotherapy group (P=0.656). While treatment-related adverse events were reported in most patients, all 25 patients completed two cycles of neoadjuvant immunotherapy and 80 of 82 patients completed two cycles of neoadjuvant chemotherapy, although one patient in the latter group died within 30 days of surgery. There was no statistically significant difference between the groups in the probability of grade 3 or higher postoperative complications within 30 days after surgery (P=0.757). CONCLUSIONS: Most patients achieved the primary and secondary endpoints of the study. However, the major pathological response (MPR) showed statistically significant differences between the neoadjuvant immunotherapy and neoadjuvant chemotherapy groups.

Background As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. Methods Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. Results circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. Conclusions Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients.

Background: Cancer-related death is mainly caused by lung adenocarcinoma (LUAD), an aggressive malignant tumor. Therefore, the identification of important LUAD-related genes and the further analysis of its prognostic significance are critical for the survival of LUAD patients.Methods: Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods were adopted to screen out TCGA-LUAD database and the gene expression profiles of GSE32863 from GEO. Functional annotation analysis and protein-protein interaction (PPI) network were conducted on differential co-expression genes. Furthermore, survival analysis was carried out on twelve hub genes that were identified by applying the CytoHubba plugin of Cytoscape. Finally, we validated the protein level of survival-related gene in HPA database.Results: A total of 358 differential co-expression genes were extracted from the database of TCGA and GEO. These genes were mainly enriched in extracellular structure organization, cell−substrate adhesion and response to acid chemical (biological process), cell−cell junction and collagen−containing extracellular matrix (cellular component), DNA−binding transcription activator activity, glycosaminoglycan binding, and growth factor binding (molecular function). In the KEGG analysis, the main pathways were Drug metabolism−cytochrome P450. Moreover, in a PPI network, the 12 hub genes (GNG11, ADRB2, ADCY4, TGFBR2, IL6, GPC3, VIPR1, GRK5, CAV1, RAMP3, RAMP2, and CALCRL) were identified. The expression level of ADCY4, VIPR1, and TGFBR2 was corresponded with clinical stages and overall survival (OS) in LUAD patients. Finally, the protein level of ADCY4 and VIPR1 was down-regulated consistently with mRNA levels in LUAD samples.Conclusion: Perhaps, ADCY4, VIPR1 and TGFBR2 play important role in tumorigenesis, so they will serve as prognostic biomarkers and therapeutic targets of LUAD in the future.

Visceral pleural invasion (VPI) has been identified as an adverse prognostic factor for non‐small cell lung cancer (NSCLC). Accurate nodal staging for NSCLC correlates with improved survival, but it is unclear whether tumors with VPI require a more extensive lymph nodes (LNs) dissection to optimize survival. We aimed to evaluate the impact of VPI status on the optimal extent of LNs dissection in stage I NSCLC, using the Surveillance, Epidemiology, and End Results (SEER) database. We identified 9297 surgically treated T1‐2aN0M0 NSCLC patients with at least one examined LNs. Propensity score matching was conducted to balance the baseline clinicopathologic characteristics between the VPI group and non‐VPI group. Log‐rank tests along with Cox proportional hazards regression methods were performed to evaluate the impact of extent of LNs dissection on survival. VPI was correlated with a significant worse survival, but there was no significant difference in survival rate between PL1 and PL2. Patients who underwent sublobectomy had slightly decreased survival than those who underwent lobectomy. Pathologic LNs examination was significantly correlated with survival. Examination of 7‐8 LNs and 14‐16 LNs conferred the lowest hazard ratio for T1‐sized/non‐VPI tumors (stage IA) and T1‐sized/VPI tumors (stage IB), respectively. The optimal extent of LNs dissection varied by VPI status, with T1‐sized/VPI tumors (stage IB) requiring a more extensive LNs dissection than T1‐sized/non‐VPI tumors (stage IA). These results might provide guidelines for surgical procedure in early stage NSCLC.

We identified and investigated the prognostic value of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD) patients and evaluate the relationship between the SPP1 expression level and clinical characteristics. First, SPP1 was identified through four LUAD datasets in GEO database and validated by the TCGA database. Then a total of 149 lung adenocarcinoma patients were included, as well as their clinicopathological characteristics collected in the study. The expression levels of SPP1 and adjacent normal tissues were assessed by immunohistochemistry. The association between SPP1 and its prognostic value was systematically evaluated. Results showed high SPP1 level predicted poorer LUAD survival by univariate Cox analysis (P = 0.017), and the multivariate result was also significant (P = 0.021). Subgroup analysis suggested the prognostic value of SPP1 was significant in stage T1 (log rank P = 0.011), stage N0 (log rank P = 0.046) and stage N1 (log rank P = 0.009) patients. After including these markers into a nomogram, the Harrell's C-index of the nomogram was 0.694. In summary, our findings suggest that SPP1 is an independent biomarker with prognostic significance in LUAD.

Lung cancer has been identified as one of the most prevalent and deadly tumors worldwide. In recent years, lncRNAs have been demonstrated to play a significant role in the development of lung cancer. Specifically, lncRNAs act as a regulator of cancer-critical genes, and they regulate the biological behavior of tumors at the transcriptional and posttranscriptional levels. Recent studies have shown that lncRNAs possess great potential in the treatment of non-small cell lung cancer patients because of their roles in diverse cellular processes, such as proliferation, metastasis, stem cell maintenance, and epithelial to mesenchymal transition, and they serve as signaling biomarkers. Compared to other invasive diagnostic methods, detection of lncRNAs may become a very useful noninvasive methodology. Moreover, lncRNAs can serve as potential therapeutic targets in non-small cell lung cancer due to their roles in regulating many signaling pathways associated with lung carcinoma. In this review, we discuss the roles and expression profile of lncRNAs. We also discuss the promising application of lncRNAs as predictors of clinical diagnosis, prognosis, and as potential therapeutic targets, aiming to demonstrate their practical value for clinical treatment.

Yang Wo, Shicheng Li, Yuanyong Wang, Tong Lu, Yi Qin, Xiao Sun, Wenjie Jiao Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China Purpose: To identify potential risk factors of lymph node metastasis and to verify the prognostic significance of the lymph node ratio (LNR) and the total number of lymph nodes examined (NNE) in tracheobronchial adenoid cystic carcinoma (ACC) patients, using a large population-based database.Patients and methods: From Surveillance, Epidemiology, and End Results database, we identified 263 patients with tracheobronchial ACC in whom complete lymph node data could be obtained. Logistic regression analysis was performed to determine predictive factors of nodal metastasis. X-tile software determined the optimal cut-off points for LNR and NNE. Kaplan–Meier analyses and Cox regression models were adopted for survival analysis.Results: Of 263 patients, 75 (28.5%) had lymph node involvement. Tumors of bronchial origin (P

BACKGROUND S100A13 plays a key role in tumor growth and metastasis. The purpose of this study was to investigate the prognostic significance of S100A13 expression, microvessel density (MVD), and survival in early stage non-small cell lung cancer (NSCLC). METHODS In silico analysis was performed to determine the associations between S100A13 and NSCLC. The data of 82 patients with early-stage NSCLC who underwent radical resection were evaluated. Paraffin-embedded tumor specimens were stained with S100A13 and CD31 (a specific endothelial marker) using immunohistochemical methods. Prognostic significance was assessed by univariate and multivariate analyses. RESULTS S100A13 messenger RNA was overexpressed in NSCLC, especially in advanced stage. Of the 82 NSCLC specimens examined, 37 (45.1%) cases exhibited S100A13 overexpression and 31 (37.8%) showed high MVD. Univariate analysis indicated that gender, age, smoking status, histology type, tumor differentiation, and T stage were not significantly associated with prognosis. However, the overall and disease-free survival rates of patients with S100A13 overexpression and high MVD were significantly lower than in the remaining cases. Multivariate analysis demonstrated that only S100A13 overexpression was an independent factor for poor prognosis in early-stage NSCLC. Statistical analysis demonstrated that the MVD was significantly higher in tumors with high (67.6%, 25/37) compared to low S100A13 expression (13.3%, 6/45) (P

BACKGROUND Increasing evidence has demonstrated that circular RNAs (circRNAs) may play an important role in oncogenesis and tumor development; however, their role in lung adenocarcinoma (LUAD) remains unclear. We identified the differentially expressed circRNAs in LUAD and investigated the potential mechanisms for cancer progression. METHODS We examined differentially expressed circRNAs in LUAD and paired normal tissues using downloaded circRNA microarrays from the Gene Expression Omnibus. We constructed gene co-expression networks based on the degree of Pearson correlation to predict the critical circRNA in LUAD. Gene Ontology analysis was performed on the genes in the network. We observed one novel circRNA upregulated in LUAD, hsa_circ_0000792, as well as its potential sponged microRNA, miR-375. Subsequent real-time quantitative PCR was used to verify the bioinformatics analysis. RESULTS Several circRNAs showed significantly different expression levels in LUAD tissues. Real-time quantitative PCR and further co-expression network analysis of 42 matched tissue samples showed a significant difference in expression between LUAD and normal tissues in hsa_circ_0000792 (P < 0.001). We built a network of hsa_circ_0000792-targeted miRNA gene interactions, including miR-375 and the corresponding messenger RNAs. Gene Ontology analysis revealed that hsa_circ_0000792 could participate in signal transduction and cell communication during LUAD development. Larger area under the curve by receiver operating characteristic curve analysis of hsa_circ_0000792 and miR-375 (0.815 and 0.772, respectively) in LUAD indicated greater potential as biomarkers. CONCLUSIONS We identified hsa_circ_0000792 as a potential LUAD biomarker; however, further studies are required to determine the mechanism of this circRNA in LUAD development.

Background The antisense of the OIP5-AS1 gene is a long non-coding RNA (lncRNA) that is reported to be upregulated and promotes cell proliferation in multiple human cancers; however, its function in lung cancer is unknown. We investigated the regulatory function and underlying mechanisms of OIP5-AS1 in lung cancer. Methods OIP5-AS1 and microRNA (miR)-378a-3p expression were assayed by quantitative real-time PCR, and proliferation-related protein expression was measured by Western blotting. Cell viability was detected using methyl thiazolyl tetrazolium assay. Luciferase reporter assay and RNA immunoprecipitation were used to detect the direct regulation of miR-378a-3p by OIP5-AS1. Nude mice were used to test the function of OIP5-AS1 in vivo. Results OIP5-AS1 was highly expressed in lung cancer tissues and was correlated with tumor size and tumor growth speed. OIP5-AS1 overexpression increased lung cancer cell proliferation in vitro. Further investigation revealed that OIP5-AS1 functions as a competing endogenous RNA of miR-378a-3p. MiR-378a-3p overexpression inhibited cell proliferation and caused proliferation-associated proteins CDK4 and CDK6 to decrease in A549 cells. Overexpression of wild type OIP5-AS1 led to strong CDK4 and CDK6 expression; however, these two proteins did not change when mutated OIP5-AS1 was upregulated. Finally, in vivo assay showed that the speed of tumor growth was increased and decreased when OIP5-AS1 was upregulated and downregulated, respectively. Conclusion Our results revealed that OIP5-AS1 acts as a growth-promoting lncRNA in lung cancer by suppressing miR-378a-3p function. OIP5-AS1 and miR-378a-3p interaction may provide a potential target for lung cancer treatment.

BACKGROUND Lung cancer (LC) is the most common malignancy in the world. Many long non-coding RNAs (lncRNAs) have been reported to be associated with LC; however, the function of KCNQ1OT1 in LC requires exploration. METHODS We conducted in silico analysis with data from The Cancer Genome Atlas to investigate the association between KCNQ1OT1 and LC. A Kaplan-Meier plotter was used to analyze the function of KCNQ1OT1 on LC patient prognosis. Quantitative reverse transcription-PCR (qRT-PCR) was performed to confirm previous results. An A549 lung cancer cell was transfected with pcDNA-KCNQ1OT1, and methyl thiazolyl tetrazolium assay was performed to investigate the function of KCNQ1OT1 on cell proliferation. in vivo assay was performed with nude mice. RESULTS Bioinformatics analysis and qRT-PCR indicated that KCNQ1OT1 expression was higher in stage I LC patients (P 0.05). KCNQ1OT1 overexpression significantly inhibited cell proliferation and tumor growth in vitro and in vivo (P

Background 99mTc bone scintigraphy (BS) is still the most common approach for the evaluation of bone metastasis in China. The purpose of this study was to investigate the necessity of BS as part of a routine preoperative workup for patients with cT1N0 subsolid lung cancer. Methods This was a prospective multicenter clinical trial (NCT03689439). Patients with cT1N0 subsolid nodules who were candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The surgical plan could be changed if a positive result was detected. The primary endpoint was the incidence rate of the surgical plan being changed because of positive BS results. The secondary endpoint was the rate of positive BS findings and the rate of related complications. Results From November 2018 to July 2019, 691 patients were enrolled into the study. None of the patients had positive BS results and no surgical plans were changed by BS findings. There were 222 male and 469 female patients. The average age was 54.8 ± 3.7 years old. The average tumor diameter was 14.9 ± 4.2 mm. There were 282 patients with pure GGO nodules and 409 with part‐solid nodules. A total of 470 patients had a single nodule, while 221 patients had multifocal lesions. The number of patients whose pathological diagnosis was invasive adenocarcinoma, minimally invasive adenocarcinoma, adenocarcinoma in situ and mucinous adenocarcinoma was 357, 293, 32 and nine, respectively. The number of patients who underwent lobectomy, segmentectomy and wedge resection was 234, 199 and 258, respectively. Conclusions 99mTc bone scintigraphy is unnecessary in the preoperative workup for patients with cT1N0 subsolid lung cancer. Key points Significant findings of the study In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings. What this study adds We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients. Clinical trial registry number: NCT03689439., In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings. We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients.

Objective The Bashang Long-tail chicken (BS), an indigenous Chinese breed, is considered cold tolerant. We selected BS, the Rhode Island Red (RIR), and their reciprocal crossbreds for the present study. The objectives were: i) to validate whether BS is cold tolerant and whether egg production and cold tolerance of crossbreds could be improved; and ii) to determine the physiological characteristics that underlie cold tolerance and favorable egg production performance in cold environments. Methods A total of 916 chickens were reared in warm and natural cold environments (daily mean ambient temperature varied from 7.4°C to 26.5°C in the warm environment and from -17.5°C to 27.0°C in the cold environment). To investigate their adaptability to the cold environment, the egg production performance and body weight were monitored and compared between breeds and environments. The cloacal temperature and serum biochemical parameters were monitored to reveal the physiological characteristics underlie cold tolerance and favorable egg production performance in the cold environment. Results The warm environment experiment showed that RIR had the highest egg production performance, and that the reciprocal crossbreds had a higher egg production performance than BS. While in the cold environment RIR had the lowest egg production performance, and the reciprocal crossbreds had a higher egg production performance than BS. In the cold environment BS and reciprocal crossbreds had higher triiodothyronine, tetraiodothyronine levels than RIR. At 35 and 39 wk of age, when the ambient temperature was extremely low (varied from -20°C to 0°C), serum glucose, follicle-stimulating hormone, luteinizing hormone, estradiol of BS and crossbreds were higher than RIR. Conclusion Bashang Long-tail chicken has a favorable cold tolerance ability. Crossbreeding with RIR and BS is an effective way to develop cold tolerant chickens with improved egg production performance.

Background Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. Methods We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein–protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Results Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein–protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Conclusion Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC.

Background HOX antisense transcript RNA (HOTAIR) is a 2148 nt long, intergenic, non-coding RNA molecule, which is reported to be highly expressed in many types of cancers. This meta-analysis summarizes its expression in cancer. Methods We searched all eligible papers on the prognostic impact of HOTAIR in cancer from inception to 30 September 2015 in PubMed, CBMdisc, and the CNKI database. Only full texts were included. Revman 5.3 was used for meta-analysis. Results A total of 11 studies of 1010 cases were included in the meta-analysis. HOTAIR expression was higher in: cancer tissues in than adjacent or normal tissues (odds ratio [OR] 37.52, 95% confidence interval [CI] 18.94–74.31; P < 0.00001); in cancer tissues with lymph node metastasis than in those without lymph node metastasis (OR 3.37, 95% CI 2.36–4.82; P < 0.00001); and in histological grades II–III than in histological gradeI(OR 0.47, 95% CI 0.29–0.75; P = 0.002). Conclusion This study shows that HOTAIR may play an important role in cancer occurrence and development, but whether it is a marker of cancer diagnosis and reliable prognosis remains to be confirmed. More rigorous design and meticulous quality epidemiological studies are required.

Background: Segmentectomy has been widely accepted as a powerful tool to treat small lung nodules. Despite been commonly used, identify the intersegment plane precisely in visual during the operation still being a complex issue. We described a novel method in minimal invasive thoracic surgery utilizing arterial- navigation combined with oxygen diffusing discrepancy based on the variance of oxygen diffusion in target and reserved segments. We perspectively analyzed 24 cases with small lung nodules of T1N0M0 disease to examine the efficacy of the new method, Methods: From June 2018 to September 2018, 24 patients with small primary lung cancers underwent segmentectomy at The Affiliated Hospital of Qingdao University. All the patients received minimally invasive procedures and standard anatomical segmentectomy. Ligation of the target segment artery followed by observation and the arterial-navigation line gradually appeared by color discrepancy in the visceral pleural surface. The plane was then testified by inflation-deflation method. Results: The mean identification time of the intersegments plane was 8 minutes. The residual segments collapsed and stayed pink, meanwhile the target parts remained inflated and turned dark. It allowed a clear identification of the intersegments plane on the surface. All operations were successfully completed. There were no perioperative deaths or major complications. The coincidence rate of arterial-navigation and inflation-deflation technique was 22/24. Conclusions: The arterial-navigation method is safe and feasible to identify the intersegmental plane in small lung tumor resection.

Non-small cell lung cancer (NSCLC) is the most common and fatal tumor worldwide, with 2.1 million new cases and 1.77 million deaths per year (1). With the wider application of examination approaches and the improvement of health awareness, higher proportions of surgically resectable early and mid-stage lung cancers have been detected. In overall, only 50% of patients have been cured after radical resection. In other cases, however, NSCLC is highly active and recurrence and/or metastasis can easily occur after surgery. In these patients, systemic therapy as a postoperative adjuvant therapy is required to eliminate or reduce residual micro-lesions to lower the risk of recurrence; meanwhile, the patients should be closely monitored to detect early recurrence. EGFR mutation is a major mutation type in lung cancer, and is seen in about 40% of lung cancer cases in Asia (2). Compared with wild types and other mutation types, EGFR-mutant NSCLC has its unique biological properties and drug susceptibilities, and thus requires specific diagnosis and treatment strategies. This expert consensus aims to review the current evidence and provide recommendations on key issues. A consensus and guideline development panel, with its members including top thoracic surgeons and oncologists all around the world, was established to decide the methodologies, processes, levels of evidence, and related recommendations. The panel members proposed the core clinical issues in the consensus document and wrote and submitted the outlines to the panel for approval. The panel carried out a problem-oriented literature search for articles published since 1997 in Chinese and foreign databases. The level of evidence was defined using the following criteria: Categories of Evidence and Consensus, Category 1: based upon high-level evidence, there is uniform consensus that the intervention is appropriate; Category 2A: based upon lower-level evidence, there is uniform consensus that the intervention is appropriate; Category 2B: based upon lower-level evidence, there is consensus that the intervention is appropriate; Category 3: based upon any level of evidence, there is major disagreement that the intervention is appropriate. The strength of recommendations was classified as strong or weak according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system (3), and the recommendation statement was composed based on the real-world evidence. A “strong” recommendation generally refers to recommendations based on high-level evidence with consistency between clinical behavior and outcome expectancy; in contrast, a “weak” recommendation is typically based on low-level evidence with uncertainty between clinical behavior and outcome expectancy. After the first draft had been completed, all the panel members were involved in revising and finalizing this document.

Lung adenocarcinoma accounts for a high proportion of lung cancers. Though efforts have been made to develop new and effective treatments for this disease, the mortality rate remains high. Gene expression microarrays facilitate the study of lung cancer at the molecular level. The present study aimed to detect differentially expressed protein-coding genes to identify novel biomarkers and therapeutic targets for lung adenocarcinoma. Aberrations in gene expression in lung adenocarcinoma were determined by analysis of mRNA microarray datasets from the Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks and statistical analysis were used to identify the biological functions of the differentially expressed genes (DEGs). The results of the bioinformatics analysis were subsequently validated using reverse transcription-quantitative PCR. A total of 303 DEGs were identified in lung adenocarcinomas, and they were enriched in a number of cancer-associated GO terms and KEGG pathways. DNA topoisomerase 2α (TOP2A), cell division cycle protein homolog 20 (CDC20), mitotic checkpoint serine/threonine protein kinase BUB1 (BUB1) and mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) exhibited the highest degree of interaction in the PPI network. Survival analysis performed using Kaplan-Meier curves and Cox regression indicated that these four genes were all significantly associated with the survival of patients with lung adenocarcinomas. In conclusion, TOP2A, CDC20, BUB1 and MAD2L1 may be key protein-coding genes that may serve as biomarkers and therapeutic targets in lung adenocarcinomas.

Background Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays a key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven to be a tumor-dependent circRNA. However, its role in non-small cell lung cancer (NSCLC) has been underreported. Methods The expression patterns of circ-ZKSCAN1 were determined using qRT-PCR in NSCLC samples and cell lines. Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. The combination of circ-ZKSCAN1 and miR-330-5p in NSCLC cells was analyzed by RNA pull-down and luciferase reporter assay. We used the bioinformatics software circbank, CircInteractome, TargetScan and Miranda to predict circRNA-miRNA and miRNA-mRNA interactions. Results Our results showed that circ-ZKSCAN1 was significantly up-regulated in NSCLC, closely related to malignant characteristics and poor prognosis, and clinically related to tumor size and clinical stage. Subsequent experiments showed that circ-ZKSCAN1 could inhibit the growth of NSCLC cells in vitro and in vivo. Importantly, circ-ZKSCAN1 can act as a sponge of carcinogenic miR-330-5p to increase the expression of FAM83A, resulting in the inhibition of MAPK signal transduction pathway, thus promoting the progress of NSCLC. Interestingly, the increase in FAM83A expression caused by circ-ZKSCAN1 overexpression could in turn promote the expression of circ-ZKSCAN1. Conclusions Circ-ZKSCAN1 is a key positive regulator of NSCLC, and clarifies the potential molecular mechanism of the new circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop in promoting the progress of NSCLC.

Background Tumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS. Materials and methods Our study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist. Results In this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis. Conclusions STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS., In this study, we retrospectively analyzed 115 patients with resected lung adenocarcinomas, aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS. We found that STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

With the rapid development of mobile communication techniques, various mobile health applications are springing up, where the single-lead atrial activity (AA) signal extraction method is urgently required. However, due to QRS residuals, the extracted AA signals by most existing methods are heavily distorted. In this paper, started from signal reconstruction perspective, a novel autoregressive (AR) model based method is presented. Two-sided AA samples around QRS segment are first modeled by AR model, and then the samples in QRS segment are reconstructed using the extrapolation formula. The experimental results on both simulated and real electrocardiograms with atrial fibrillation show that, after using the proposed method, QRS residuals were significantly reduced.

BACKGROUND: Robotic lobectomy is widely used for lung cancer treatment. So far, few studies have been performed to systematically analyze the learning curve. Our purpose is to define the learning curve to provide a training guideline of this technique. METHODS: A total of 208 consecutive patients with primary lung cancer who underwent robotic-assisted lobectomy by our surgical team were enrolled in this study. Baseline information and postoperative outcomes were collected. Learning curves were then analyzed using the cumulative sum (CUSUM) method. Patients were divided into three groups according to the cut-off points of the learning curve. Intraoperative characteristics and short-term outcomes were compared among the three groups. RESULTS: CUSUM plots revealed that the docking time, console time and total surgical time in patients were 20, 34 and 32 cases, respectively. Comparison of the surgical time among the 3 phases revealed that the total surgical time (197.03±27.67, 152.61±21.07, 141.35±29.11 min, P

A large proportion of all life on Earth lives in the ocean. Marine life includes microscopic life, plants, algae, invertebrates, fungi, and vertebrates. Due to the high salinity, high pressure, hypoxic and low temperature of the marine environment, the polysaccharides or glycans synthesized by marine life have diverse structures and unique biological activities that are not found in glycans in terrestrial life. Moreover, the glycans are the most abundant biopolymers made by the marine life. The reported activities of marine glycans include but not limit to anticoagulant, antithrombotic, antitumor, antioxidant, antiviral, and antibacterial activities. Published reports on marine glycans have increased more than threefold during the past decade. Meanwhile, several pharmaceutical companies in different countries have invested in the research and development of marine glycan-based drugs. Propylene glycol alginate sodium sulfate (PSS), the first marine glycan-based drug developed in China approved by the Chinese FDA, has been used in the treatment of cardiovascular and other diseases for more than 30 years. In this chapter, the structural characteristics, pharmacological activities and clinical applications of three Chinese FDA approved and commercially available marine glycan-based drugs (PSS, PGMS, and FPS) and five marine glycan-based drugs at different stages of clinical studies (GV971, 911, PGS, PS916, and HS203) in China will be reviewed and discussed. Understanding the marine glycan-based drugs at structure and function level would be needed to comprehend their clinical efficacy. Such knowledge will provide molecular basis for the future research and development of marine glycan-based drugs world widely.

The mechanisms underlying the oncogenesis and progression of lung adenocarcinoma (LUAD) are currently unclear. The discovery of competitive endogenous RNA (ceRNA) regulatory networks has provided a new direction for the treatment and prognosis of patients with LUAD. However, the mechanism of action of ceRNA in LUAD remains elusive. In the present study, differentially expressed mRNAs, microRNAs (miRs) and long non-coding RNAs from the cancer genome atlas database were screened. CeRNAs for LUAD were then identified using online prediction software. Among the ceRNAs identified, family with sequence similarity 83 member A (FAM83A), miR-34c-5p, KCNQ1OT1 and FLJ26245 were observed to be significantly associated with the overall survival of patients with LUAD. Of note, FAM83A has potential significance in drug resistance, and may present a candidate biomarker for the prognosis and treatment of patients with LUAD.

8524 Background: Neoadjuvant treatment has demonstrated efficacy in several types of cancer and is increasingly used for the treatment of early-stage cancers with the potential of cancer downstaging to enhance complete surgical resection and to improve clinical outcomes. Recent evidences have demonstrated that the neoadjuvant use of first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may provide clinically meaningful improvement in EGFRm non-small cell lung cancer (NSCLC) patients, however, limited data were reported on osimertinib, the third-generation EGFR-TKI, in the neoadjuvant setting. Here we present an interim analysis of osimertinib as neoadjuvant treatment for resectable EGFRm NSCLC. Methods: NEOS is a prospective, multi-center, single-arm study to evaluate the efficacy and safety of osimertinib as neoadjuvant treatment in resectable EGFRm (19del/L858R) lung adenocarcinoma. Eligible patients were treated with osimertinib 80 mg orally per day for six weeks followed by surgery. Assessment of response to neoadjuvant therapy was performed according to RECIST 1.1. The primary endpoint was response rate. Secondary endpoints included safety, R0 surgical resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate. Results: As of Dec. 17, 2020, 18 eligible patients (median age 61 [range 46-73], 27.8% male, 22.2% ECOG PS 1) have been enrolled. Patients with clinical stages IIa, IIb, and IIIa (8th AJCC) accounted for 16.7%, 22.2% and 61.1%, respectively. Half (9/18) of the patients had EGFR exon 21 L858R mutations and the other half (9/18) had EGFR exon 19del mutations. Amongst all 15 patients who completed efficacy assessment after neoadjuvant osimertinib, the response rate (RR) was 73.3% (11/15) and the disease control rate (DCR) was 100% (15/15). R0 surgical resection was performed in 93.3% (14/15) patients. Pathological downstaging occurred in 53.3% (8/15) patients. 42.9% (3/7) of the patients with confirmed N2 lymph nodes experienced downstaging to N0 disease after receiving neoadjuvant osimertinib. One patient was identified with a pCR. Adverse events (AEs) were reported in 66.7% (12/18) of patients, with the most common AE being rash (8/18, 44.4%), oral ulceration (8/18, 44.4%), and diarrhea (5/18, 27.8%). No grade 3-5 AEs or serious AEs were reported. Conclusions: Interim analysis from this study indicated neoadjuvant osimertinib as an effective and feasible treatment in patients with resectable stage II-IIIB EGFRm NSCLC. The trial is ongoing and the final results will be provided in the future. Clinical trial information: ChiCTR1800016948.

Activation of epidermal growth factor receptor signaling by kinase dimerization plays a crucial role in the development, progression, and metastasis of lung cancer. Tumor suppressor Mig-6 is a natural inhibitory protein of epidermal growth factor receptor signaling; the protein uses its two regions, namely segments 1 and 2, to directly interact with kinase dimerization interface and then inactivates the kinases. Here, we attempted to improve the binding capability of isolated segment 2 peptide to epidermal growth factor receptor family kinases by cyclizing the peptide. In the procedure, a disulfide bond was introduced across two ends of the peptide to constrain the peptide conformation in an antiparallel, double-stranded β-sheet. Molecular dynamics simulations indicated high-structural flexibility and intrinsic disorder associated with the linear peptide of Mig-6 segment 2, whereas its cyclized version exhibited a considerable rigidity and low mobility. Molecular mechanics/Poisson–Boltzmann surface area calculations and quasiharmonic analysis revealed that the cyclization influences kinase–peptide interaction enthalpy modestly, but can largely minimize entropy penalty upon the interaction, thus effectively restoring peptide binding free energy. Fluorescence polarization assays found no affinity of linear peptide to epidermal growth factor receptor family kinases, while a weak or moderate affinity can be observed for cyclic peptide binding to the kinases.

Double-sleeve lobectomy, which includes bronchoplasty and pulmonary arterial angioplasty, is required for certain cases of central-type lung cancer. It is usually done by open surgery or video-assisted thoracoscopic surgery (VATS). In recently, da Vinci system and robotic surgery have been applied in such complicated cases. Here we describe the details associated with robotic-assisted double-sleeve lobectomy.

Background Although video-assisted thoracoscopic surgery (VATS) has been widely applied to both peripheral and central lung cancer treatment in many centers, there is great hesitation to adopt it for carinal or tracheal surgical procedures. The aims of this study were to explore the feasibility of VATS in the treatment of benign and malignant diseases involving the carina and trachea and to highlight relevant techniques. Methods Patients undergoing VATS carinal or tracheal procedures between May 2012 and July 2015 from three centers in China were included in this study. Their clinical characteristics, operative details, and postoperative course were analyzed. Results Twelve patients underwent five different types of VATS airway reconstructions with or without lobectomy: including right bronchial resection with partial carinal reconstruction (3 patients), tracheal resection and reconstruction (4 patients), tracheal or right bronchial resection with carinal reconstruction (3 patients), left bronchial resection with carinal reconstruction (1 patient), and right pneumonectomy with carinal reconstruction (1 patient). Complete resection was achieved in all patients. The mean operative time was 224 ± 78 minutes, and the median time of the first anastomosis was 41 minutes (range, 15 to 60 minutes), regardless of whether the reconstruction was a tracheal or carinal. The median estimated blood loss was 100 mL (range 10 to 1000 mL). The mean postoperative hospital stay was 12.5 ± 2.5 days. There was no perioperative mortality or major morbidity. Median duration of follow-up was 12 months (range 5 to 43 months). Conclusions VATS resection and reconstruction of the carina or trachea are feasible, and these procedures can be safely performed using the techniques described. We believe, with the accumulation of VATS experience, these procedures could be adopted as routine approaches in tracheal surgery.

We describe a novel method using electromagnetic navigation bronchoscopy (ENB) without dye marking to perform vectorial localization for an impalpable peripheral lesion in the right lower lobe during diagnostic surgical resection in a 52-year-old woman. After the ENB registration process, the anesthetist changed the single-lumen endotracheal tube to a double-lumen endobronchial tube. Guided by the ENB system, the operator delivered the probe of the locatable guide to the planned site through the right lumen of the endobronchial tube. The ENB system allows calculation of the direction and distance between the probe and the lesion, confirming the relative location of the lesion. The locatable guide was retained during surgery as an intraoperative indicator, rather than applying dye marking. During video-assisted thoracoscopic surgery, the protuberant visceral pleura poked by the probe accurately indicated the relative location of the lesion. Accordingly, we performed precise wedge resection for diagnosis, followed by lobectomy, resulting in a diagnosis of invasive adenocarcinoma. Vectorial localization is an alternative method of ENB-guided localization to peripheral pulmonary lesions, which can provide the accurate location of such lesions for diagnostic surgical resection.

An exclusive right thoracic approach for esophagus surgery is rarely used, with few reports of its use in China. We retrospectively reviewed the data of 21 esophageal cancer patients from January 2010 to January 2015. Their age ranged from 74-83 years (average 76.6). All of the patients had lower pulmonary function. After multidisciplinary team discussion, sufficient preoperative preparation, and assessment of cardiopulmonary reserve, an exclusive right thoracic approach for esophageal cancer resection was performed. The esophagus was dissected in the right chest and the stomach was separated through the esophageal hiatus. The tube stomach and the esophageal remnant were anastomosed with a stapling device at the top of the right side of the thoracic cavity. All operations were successfully completed; however, there were two early postoperative deaths resulting from pulmonary infection and pulmonary artery embolism. The one-year postoperative survival rate was 66.7%. An exclusive right thoracic approach could be selectively used for elderly patients with poor pulmonary function.

Objective To evaluate the surgical and oncologic outcomes of robotic sleeve lobectomy in comparison with video-assisted thoracoscopic surgery (VATS) and open surgery. Methods Surgical outcomes in patients with non–small cell lung cancer who underwent sleeve lobectomy via robotic, VATS, and thoracotomy were assessed using the χ2 test, Fisher exact test, and the Kruskal–Wallis rank sum test. Log-rank test and Cox proportional hazards model were used in survival analyses. Propensity score–weighted matching was used to achieve the balance of baseline among the 3 groups. Results Between 2012 and 2017, 188 patients were included and divided into robotic (n = 49), VATS (n = 73), and open (n = 66) groups. After weighted matching that retained all patients, no statistical difference in 90-day mortality or morbidity among the 3 groups was shown. Patients in the robotic group had less bleeding loss (P .050). Conclusions Robotic sleeve lobectomy is a safe, feasible, and effective procedure. Compared with VATS and open techniques, robotic sleeve lobectomy has a similar oncologic prognosis for patients with centrally located non–small cell lung cancer. Further studies with a larger sample size and long-term follow-up are needed.

Background: Tumor spread through air spaces (STAS) was recently reported as a novel risk factor for the prognosis of patients with resected lung adenocarcinoma that indicates invasive tumor behavior. The purpose of this study was to investigated the relationship between Twist, Slug with STAS in surgically resected lung adenocarcinoma and aimed to characterize the potential connection between epithelial-mesenchymal transition (EMT) and STAS. Methods: A total of 115 patients with resected lung adenocarcinomas were analyzed retrospectively to evaluate the relationship between Twist, Slug with STAS. Findings: STAS was observed in 56 (48.7%) patients. There were significant correlations between the presence of tumor STAS with Twist / Slug overexpression. The logistic model further revealed that pathological stage, Twist / Slug overexpression were independent risk factors for STAS. A multivariate analysis contained pathologic stage, STAS, Twist / Slug overexpression, showed that pathologic stage and STAS were independent prognostic factors for poor RFS/OS. The other multivariate model contained pathologic stage, Twist / Slug overexpression, showed that pathologic stage and Twist / Slug overexpression were independent prognostic factors for poor RFS/OS. Interpretation: STAS was correlated with overexpression of Twist / Slug, which could potentially provide information on the mechanism of STAS. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interest: The authors have no conflicts of interest to declare. Ethical Approval: The Institutional Review Board of Affiliated Hospital of Qingdao University approved this retrospective study (IRB#QYFYKY 2018-10-11-2). Informed consent was waived by the institutional review board because this was a retrospective study.

A large proportion of all life on Earth lives in the ocean. Marine life includes microscopic life, plants, algae, invertebrates, fungi, and vertebrates. Due to the high salinity, high pressure, hypoxic and low temperature of the marine environment, the polysaccharides or glycans synthesized by marine life have diverse structures and unique biological activities that are not found in glycans in terrestrial life. Moreover, the glycans are the most abundant biopolymers made by the marine life. The reported activities of marine glycans include but not limit to anticoagulant, antithrombotic, antitumor, antioxidant, antiviral, and antibacterial activities. Published reports on marine glycans have increased more than threefold during the past decade. Meanwhile, several pharmaceutical companies in different countries have invested in the research and development of marine glycan-based drugs. Propylene glycol alginate sodium sulfate (PSS), the first marine glycan-based drug developed in China approved by the Chinese FDA, has been used in the treatment of cardiovascular and other diseases for more than 30 years. In this chapter, the structural characteristics, pharmacological activities and clinical applications of three Chinese FDA approved and commercially available marine glycan-based drugs (PSS, PGMS, and FPS) and five marine glycan-based drugs at different stages of clinical studies (GV971, 911, PGS, PS916, and HS203) in China will be reviewed and discussed. Understanding the marine glycan-based drugs at structure and function level would be needed to comprehend their clinical efficacy. Such knowledge will provide molecular basis for the future research and development of marine glycan-based drugs world widely.

Additional file 2: Figure S1. The methylmix model of the rest of methylation-driven genes in ESCC.