The predictive value of serum tumor markers for EGFR mutation in non-small cell lung cancer patients with non-stage IA.

Objective: The predictive value of serum tumor markers (STMs) in assessing epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC), particularly those with non-stage IA, remains poorly understood. The objective of this study is to construct a predictive model comprising STMs and additional clinical characteristics, aiming to achieve precise prediction of EGFR mutations through noninvasive means. Materials and methods: We retrospectively collected 6711 NSCLC patients who underwent EGFR gene testing. Ultimately, 3221 stage IA patients and 1442 non-stage IA patients were analyzed to evaluate the potential predictive value of several clinical characteristics and STMs for EGFR mutations. Results: EGFR mutations were detected in 3866 patients (57.9 %) of all NSCLC patients. None of the STMs emerged as significant predictor for predicting EGFR mutations in stage IA patients. Patients with non-stage IA were divided into the study group (n = 1043) and validation group (n = 399). In the study group, univariate analysis revealed significant associations between EGFR mutations and the STMs (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin-19 fragment (CYFRA21-1)). The nomogram incorporating CEA, CYFRA 21-1, pathology, gender, and smoking history for predicting EGFR mutations with non-stage IA was constructed using the results of multivariate analysis. The area under the curve (AUC = 0.780) and decision curve analysis demonstrated favorable predictive performance and clinical utility of nomogram. Additionally, the Random Forest model also demonstrated the highest average C-index of 0.793 among the eight machine learning algorithms, showcasing superior predictive efficiency. Conclusion: CYFRA21-1 and CEA have been identified as crucial factors for predicting EGFR mutations in non-stage IA NSCLC patients. The nomogram and 8 machine learning models that combined STMs with other clinical factors could effectively predict the probability of EGFR mutations.

Randomized Trial of Modified Chest Tube Placement vs Routine Placement After Lung Resection.

BACKGROUND: Chest tube placement after pulmonary resection is usually considered a mandatory procedure. However, peritubular leakage of pleural fluid and intrathoracic air is frequent after surgery. Therefore, we separated the chest tube from the intercostal space as a modified placement strategy. METHODS: Patients undergoing robotic and video-assisted lung resection were enrolled in this study at our medical center between February 2021 and August 2021. All patients were randomly divided into either the modified group (n = 98) or the routine group (n = 101). The incidence of peritubular leakage of pleural fluid and peritubular air leaking or entering after surgery were the primary end points of the study. RESULTS: A total of 199 patients were randomized. Patients in the modified group had lower incidence of peritubular leakage of pleural fluid (after surgery, 39.6% vs 18.4% [P = .001]; after chest tube removal, 26.7% vs 11.2% [P = .005]), lower incidence of peritubular air leaking or entering (14.9% vs 5.1% [P = .022]), and fewer dressing changes (5.02 ± 2.30 vs 3.48 ± 0.94 [P < .001]). In patients undergoing lobectomy and segmentectomy, the type of chest tube placement was associated with the severity of peritubular pleural fluid leakage (P < .05). CONCLUSIONS: The modified chest tube placement was safe and had better clinical efficacy than the routine type. The reduction of postoperative peritubular leakage of pleural fluid resulted in better wound recovery. This modified strategy should be popularized, especially in patients undergoing pulmonary lobectomy or segmentectomy.

Process and Eco-Environment Impact of Land Use Function Transition under the Perspective of "Production-Living-Ecological" Spaces-Case of Haikou City, China.

Land use function transition can change the eco-environment. To achieve an "Intensive and efficient production space, moderately livable living space, and beautiful ecological space", the ecological effects of land use function transition in the context of ecologically fragile areas and rapidly developing areas of socio-economic importance need to be studied. In this study, from the perspective of "production-living-ecological" spaces, we calculated the index of regional eco-environment quality, positive and negative effects of eco-environment impact, and the ecological contribution rate and analyzed the driving factors. We found the following: (1) The production space was greatly compressed, living space was expanded, and ecological space was significantly squeezed. Haikou underwent a rapid transformation from an agriculture-dependent city to an industrial city. Land supply for urban and rural living was guaranteed by the Chinese land management department. However, Haikou prioritized economic development over environmental protection. (2) The regional eco-environment quality index decreased from 2009 to 2018. The expansion of pasture-based ecological spaces is important for improving the quality of the eco-environment, and the reduction of forest ecological space strongly influences the deterioration of the eco-environment. (3) Resource base, historical level of utilization, suitability of land, the ecological value potentiality, and regional policies greatly affected land use function transition and its eco-environment. (4) Refining the planning of territorial space, comprehensively improving land and resources, and reforming the rural land system greatly influenced policy guidance and technical regulation for coordinating "production-living-ecological" spaces and improving the regional eco-environment. In this study, we tested the effect of regional policy regulation on land use function transition and provided a reference for coordinating "production-living-ecological" spaces.

Development and validation of a prognostic risk signature for lung adenocarcinoma constructed by six ferroptosis, necroptosis, and pyroptosis-related lncRNAs.

Background: Identifying populations that benefit from immune checkpoint blockade (ICB) therapy remains a major challenge in the treatment of lung adenocarcinoma (LUAD). Existing programmed cell death (PCD) related prognostic models only consider a single mechanism, such as ferroptosis, necroptosis, and pyroptosis, and do not reflect the interaction of multiple mechanisms. This study aims to explore lncRNAs associated with multiple modes of PCD and reveal a risk signature to assess prognosis and treatment outcomes in LUAD patients. Methods: Based on expression data in The Cancer Genome Atlas (TCGA) database, ferroptosis, necroptosis, and pyroptosis-related lncRNAs (FNPRlncRNAs) were obtained by taking the intersection of ferroptosis-related lncRNAs (FRlncRNAs), necroptosis-related lncRNAs (NRlncRNAs), and pyroptosis-related lncRNAs (PRlncRNAs) differentially expressed in LUAD and normal tissues. Patients with complete survival information and expression data from TCGA database were randomly assigned to training and testing sets (1:1). Univariate, LASSO, and multivariate Cox regression analyses were performed on the training set, and a risk signature was established. Kaplan-Meier survival curves were used to verify the prognostic ability of risk signature, and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy. We then analyzed molecular and immune profile differences between high and low-risk subgroups. T-cell dysfunction and Exclusion (TIDE) scores were used to assess the response to immunotherapy in each risk subgroup. Finally, three LUAD clusters (C1, C2, and C3) were identified according to the risk signature. Results: Patients in the low-risk subgroup had higher overall survival (OS) than that in the high-risk subgroup in the K-M survival curve. The area under ROC curves (AUC) of 1-, 3-, and 5-year ROC were 0.742, 0.762, and 0.749 in the training set, and 0.672, 0.642, and 0.563 in the testing set, respectively. Compared with the high-risk subgroup, patients in the low-risk subgroup have beneficial tumor immune microenvironment and molecular characteristics, but are less likely to benefit from immunotherapy. Finally, the three LUAD clusters (C1, C2, C3) identified by risk signature had different responses to drug treatment. Conclusions: The prognosis risk signature constructed using FNPRlncRNAs is helpful to predict the prognosis of LUAD and may contribute to its individualized treatment.

The long-term oncologic outcomes of robot-assisted bronchial single sleeve lobectomy for 104 consecutive patients with centrally located non-small cell lung cancer.

Background: Up to now, no study has described the long-term survival and its prognostic factors of robot-assisted sleeve lobectomy. Here, the present cohort study reported the long-term oncologic outcomes of robot-assisted sleeve lobectomy to evaluate the oncological feasibility of sleeve lobectomy via a robotic surgical system in patients with centrally located non-small cell lung cancer (NSCLC). Methods: A total of 104 consecutive patients with centrally located NSCLC who underwent robot-assisted bronchial single sleeve lobectomy between October 2014 and May 2021 were retrospectively reviewed. Bronchial single sleeve lobectomy only refers to the resection and end-to-end anastomosis reconstruction of the bronchus, without the resection of the pulmonary vessels or carina. The recurrence status during follow-up, 5-year overall survival (OS) and disease-free survival (DFS) were assessed. Results: In the total cohort, 47 (45.2%) patients had pathological stage I disease, 28 (26.9%) patients had pathological stage II disease, and 29 (27.9%) patients had pathological stage III disease. Recurrence occurred in 26 (25.0%) patients, including locoregional recurrence in 10 (9.6%) patients and distant recurrence in 16 (15.4%) patients. No endobronchial nor perianastomotic recurrence was detected. The Kaplan-Meier curves indicated that the 5-year DFS and OS rates in the cohort were 67.9% and 73.0%, respectively. In terms of pathological stages, the 5-year DFS and OS rates were 82.9% and 82.2% for stage I patients, 57.8% and 69.7% for stage II patients, and 54.5% and 63.7% for stage III patients, respectively. Multivariable analyses demonstrated that higher pathological stage or N2 stage were independent risk factors for poorer DFS and OS. Conclusions: Robot-assisted bronchial single sleeve lobectomy could be an oncologically adequate procedure for patients with centrally located NSCLC, due to the long-term survival was similar to that reported for video-assisted thoracoscopic surgery (VATS) or open technique. Further studies of comparative studies or high-quality randomized controlled trials are required.

Assessment and dynamic mechanisms of the land-use dominant morphology transition: a case study of Hainan Province, China.

This paper was aimed at providing a perspective on the assessment of land-use dominant transition. Based on the transfer matrix of land-use type, the dynamic degree of dominant morphology transition was measured, and an active degree index was proposed. The spatiotemporal differentiation characteristics were assessed and analyzed by land use change characteristics in different phases. Our assessment resulted in three types of spatiotemporal differentiation of Hainan Province in China. The whole island can be divided into three regions with two parallel lines at 45° based on spatiotemporal differentiation characteristics. The "slow-type" was distributed in four eastern counties (cities), "steady-type" was distributed in 13 central and western counties (cities), and the "active-type" was distributed in four central counties (cities). Over three phases, namely 2010-2011, 2012-2015, and 2015-2018, four levels of spatiotemporal differentiation of the 21 counties (cities) were assessed, and they were relatively stable, leaping, declining, and unstable. Areas of new construction and fixed assets investments consumed by increased construction land were the positive factors of land-use dominant transition, while output values of secondary industries and area of industrial-mining per capita were the negative factors. Based on these results, a more informative examination of LULC was proposed, and all resulting land management policies will be more targeted and effective.

Single utility port approach in robot-assisted sleeve segmentectomy for bronchial carcinoid tumor.

Bronchial carcinoid tumors are low-grade malignant and lung-sparing surgery is preferred for the removal of these tumors. We describe a surgical technique of robot-assisted sleeve segmentectomy via single utility port approach with three robotic arms. This operation was performed in an aged patient with decreased pulmonary function, whose carcinoid tumor was located at the origin of the right superior segmental bronchus. A 1.5-cm incision was performed in the eighth intercostal space of the midaxillary line and another 4-cm incision was made in the fifth intercostal space of the anterior axillary line. Postoperative recovery of the patient was smooth without postoperative complications.

Systems biomarker characteristics of circulating alkaline phosphatase activities for 48 types of human diseases.

BACKGROUND: Most human diseases are accompanied by systems changes. Systems biomarkers should reflect such changes. The phosphorylation and dephosphorylation of biomolecules maintain human homeostasis. However, the systems biomarker characteristics of circulating alkaline phosphatase, a routine blood test conducted for many human diseases, have never been investigated. METHOD: This study retrieved the circulating alkaline phosphatase (ALP) activities from patients with 48 clinically confirmed diseases and healthy individuals from the database of our hospital during the past five years. A detailed analysis of the statistical characteristics of ALP was conducted, including quantiles, receiving operator curve (ROC), and principal component analysis. RESULTS: Among the 48 diseases, 45 had increased, and three had decreased median levels of ALP activities compared to the healthy control. Preeclampsia, hepatic encephalopathy, pancreatic cancer, and liver cancer had the highest median values, whereas nephrotic syndrome, lupus erythematosus, and nephritis had decreased median values compared to the healthy control. Further, area under curve (AUC) values were ranged between 0.61 and 0.87 for 19 diseases, and the ALP activities were the best systems biomarker for preeclampsia (AUC 0.87), hepatic encephalopathy (AUC 0.87), liver cancer (AUC 0.81), and pancreatic cancer (AUC 0.81). CONCLUSIONS: Alkaline phosphatase was a decent systems biomarker for 19 different types of human diseases. Understanding the molecular mechanisms of over-up-and-down-regulation of ALP activities might be the key to understanding the whole-body systems' reactions during specific disease progression.

Predictive value of a novel Asian lung cancer screening nomogram based on artificial intelligence and epidemiological characteristics.

BACKGROUND: To develop and validate a risk prediction nomogram based on a deep learning convolutional neural networks (CNN) model and epidemiological characteristics for lung cancer screening in patients with small pulmonary nodules (SPN). METHODS: This study included three data sets. First, a CNN model was developed and tested on data set 1. Then, a hybrid prediction model was developed on data set 2 by multivariable binary logistic regression analysis. We combined the CNN model score and the selected epidemiological risk factors, and a risk prediction nomogram was presented. An independent multicenter cohort was used for model external validation. The performance of the nomogram was assessed with respect to its calibration and discrimination. RESULTS: The final hybrid model included the CNN model score and the screened risk factors included age, gender, smoking status and family history of cancer. The nomogram showed good discrimination and calibration with an area under the curve (AUC) of 91.6% (95% CI: 89.4%-93.5%), compare with the CNN model, the improvement was significance. The performance of the nomogram still showed good discrimination and good calibration in the multicenter validation cohort, with an AUC of 88.3% (95% CI: 83.1%-92.3%). CONCLUSIONS: Our study showed that epidemiological characteristics should be considered in lung cancer screening, which can significantly improve the efficiency of the artificial intelligence (AI) model alone. We combined the CNN model score with Asian lung cancer epidemiological characteristics to develop a new nomogram to facilitate and accurately perform individualized lung cancer screening, especially for Asians.

Perioperative safety and feasibility outcomes of stage IIIA-N2 non-small cell lung cancer following neoadjuvant immunotherapy or neoadjuvant chemotherapy: a retrospective study.

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/m2 gemcitabine and 80 mg/m2 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.

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p.

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.

Circ-AASDH functions as the progression of early stage lung adenocarcinoma by targeting miR-140-3p to activate E2F7 expression.

BACKGROUND: Lung adenocarcinoma (LUAD), which is the most common subtype of non-small cell lung cancer, is a leading course of cancer-related mortality worldwide. Recently, circular RNA (CircRNAs) has become a hot spot in cancer research because of its important role in tumorigenesis and development and its superior stability. This study aims to clarify the role of circ-AASDH in LUAD and explore its competitive endogenous RNA mechanism. METHODS: The circ-AASDH, miR-140-3p and E2F transcription factor 7 (E2F7) mRNA expression levels were detected via qRT-PCR. CCK-8 and colony formation assay were used to evaluate the ability of cell proliferation. Transwell assay and wound healing assay were performed to measure the invasion and migration ability. Flow cytometry was used to detect the apoptosis of cells. Moreover, Sanger sequencing, RNaseR treatment and divergent primers were used to verify the circular structure. Luciferase reporter and RNA pull-down experiment were performed to characterize the ceRNA mechanism of circ-AASDH. The xenograft model of mice was established to investigate the tumorigenicity of circ-AASDH to LUAD in vivo. RESULTS: By screening for differentially expressed circRNAs, we found that circ-AASDH was highly expressed in LUAD tissues and cells and correlated with tumor size, clinical stage and poor prognosis. Transfection of si-circ-AASDH can inhibit the proliferation and migration of LUAD cells and promote apoptosis in vitro. In mechanism, circ-AASDH could be used as a sponge of miR-140-3p to weaken its inhibition on the expression of E2F7. Additionally, the overexpression of circ-AASDH could deduce the suppression of miR-140-3p on the malignant progression of LUAD cells. Besides, silencing of circ-AASDH inhibited cell proliferation and migration by regulating the expression of E2F7. Furthermore, overexpression of circ-AASDH can promote the growth of LUAD in vivo. CONCLUSIONS: Circ-AASDH/miR-140-3p/E2F7 regulating axis promoted the progression in LUAD. Our results provided ideas for understanding the biological mechanism of circ-AASDH and clarify potential therapeutic targets in LUAD.

Effects of Ten-Eleven Translocation-2 (Tet2) on myogenic differentiation of chicken myoblasts.

Skeletal muscle development is an orchestrated progress that is primarily regulated by temporospatial expression of myogenic regulatory factors (MRFs). Recent studies demonstrated that DNA demethylation also exerted a critical role in myogenesis. However, the function of Tet2 in the regulation of chicken myogenesis still remains unknown. In the present study, the role of Tet2 in regulating myogenic differentiation was determined by using a model of primary myoblasts from chickens. The expression of Tet2 was significantly elevated during myoblast differentiation. Meanwhile, the level of 5hmC in genomic DNA was increased, but H3K9me2 and H3K27me3 were markedly reduced following differentiation. Knockdown of Tet2 significantly inhibited the formation of multinucleated myotubes, which was accompanied by a reduction of relevant pivotal MRFs. Moreover, the level of 5hmC decreased sharply in Tet2 knockdown myoblasts. Attenuated differentiated myoblasts that resulted from reduced Tet2 also demonstrated an increased level of H3K9me2 and H3K27me3. Collectively, these results indicated that Tet2 played an essential role during myogenesis, which affected demethylation of genomic DNA and histone to regulate expression of MRFs and therefore, contributed to myoblast differentiation.

Different efficacy in the non-small cell lung cancer patient with bilateral synchronous lesions treated with neoadjuvant gefitinib therapy: a case report.

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.

Antibiotics promote abdominal fat accumulation in broilers.

Antibiotics stimulate the growth of animals but result in drug residues and bacterial resistance. In this study, the negative effect of antibiotics on abdominal fat deposition was evaluated in broilers. The results showed that adding both chlortetracycline (50 g/1,000 kg) and tylosin (50 g/1,000 kg) significantly increased abdominal fat weight, abdominal fat percentage (p < .05), and triglyceride and cholesterol levels (p < .05) in blood. Also, both products synchronously stimulated intestinal absorption and synthesis of liver fat. The expression levels of the peroxisome proliferator-activated receptor Î³ (PPARγ), diacylgycerol acyltransferase 2 (DGAT2), lipoprotein lipase (LPL), and fatty acid-binding protein (FABP4) genes in abdominal fat tissue significantly increased (p < .05 or 0.01) when antibiotics were added to the feed. However, no significant difference was found in expression of the fatty acid synthesis (FAS) or acetyl CoA carboxylase (ACC) genes. Further in vitro study results revealed that antibiotics had no effect on fat content or the related gene expression levels in preadipocytes. In summary, the antibiotics induced fat deposition in adipose tissues by activating extracellular absorption of fatty acids from intestinal absorption and synthesis of liver fat. However, it shows no direct regulation by adipose tissue.

Identification of the Differentially Expressed Genes of Muscle Growth and Intramuscular Fat Metabolism in the Development Stage of Yellow Broilers.

High-quality chicken meat is an important source of animal protein for humans. Gene expression profiles in breast muscle tissue were determined, aiming to explore the common regulatory genes relevant to muscle and intramuscular fat (IMF) during the developmental stage in chickens. Results show that breast muscle weight (BMW), breast meat percentage (BMP, %), and IMF (%) continuously increased with development. A total of 256 common differentially expressed genes (DEGs) during the developmental stage were screened. Among them, some genes related to muscle fiber hypertrophy were upregulated (e.g., CSRP3, LMOD2, MUSTN1, MYBPC1), but others (e.g., ACTC1, MYL1, MYL4) were downregulated from Week 3 to Week 18. During this period, expression of some DEGs related to the cells cycle (e.g., CCNB3, CCNE2, CDC20, MCM2) changed in a way that genetically suggests possible inhibitory regulation on cells number. In addition, DEGs associated with energy metabolism (e.g., ACOT9, CETP, LPIN1, DGAT2, RBP7, FBP1, PHKA1) were found to regulate IMF deposition. Our data identified and provide new insights into the common regulatory genes related to muscle growth, cell proliferation, and energy metabolism at the developmental stage in chickens.

Testosterone Promotes the Proliferation of Chicken Embryonic Myoblasts Via Androgen Receptor Mediated PI3K/Akt Signaling Pathway.

Testosterone (T) is essential for muscle fiber formation and growth. However, the specific mechanism by which T regulates skeletal muscle development in chicken embryos remains unclear. In this study, the role of T in myoblast proliferation both in vivo and in vitro was investigated. Results showed that the T administration significantly increased the ratio of breast muscle and leg muscle. T induced a significant increase in the cross-sectional area (CSA) and density of myofiber and the ratio of PAX7-positive cells in the skeletal muscle. Exogenous T also induced the upregulation of myogenic regulatory factors (MRFs) and cyclin-dependent kinases (CDK2)/Cyclin D1 (CCND1) and protein levels of androgen receptor (AR), p-Akt and PAX7. Furthermore, T treatment significantly promoted myoblasts cultured in vitro entering a new cell cycle and increased PAX7-positive cells. The mRNA and protein expression of AR and PAX7 were upregulated when treated with T compared to that of the control. The addition of T induced proliferation accompanied by increasing AR level as well as PI3K (Phosphoinositide 3-kinase)/Akt activation. However, T-induced proliferation was attenuated by AR, PI3K, and Akt-specific inhibitors. These data indicated that the pro-proliferative effect of T was regulated though AR in response to the activation of PI3K/Akt signalling pathway.

[A Review of EGFR-TKIs Therapy of Non-small Cell Lung Cancer
with Uncommon EGFR Mutations].

Lung cancer is the most common cancer and the leading cause of cancer death. Non-small cell lung cancer (NSCLC) represents over 85% of all lung cancers, and up to 50% of Asian NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations. A number of studies have consistently demonstrated that uncommon EGFR-mutated NSCLC patients treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve better survival outcomes. However, because uncommon EGFR mutations are generally associated with reduced sensitivity to EGFR-TKIs, which will bring a negative impact on the result of the study, the majority of clinical trials investigating the efficacy of EGFR-TKIs have included only patients with common EGFR mutations. In addition, uncommon EGFR mutations are rare in themselves, leading to the small number of such patients enrolled in these trials. Due to the small number and highly heterogeneous sensitivity of uncommon EGFR mutations, the efficacy of EGFR-TKIs in patients harboring uncommon EGFR mutations remains elusive. This article reviews the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations, and give some reasonable advice about the selection of treatments for patients with NSCLC who harbor uncommon EGFR mutations.

Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

BACKGROUND: Aberrant DNA methylations are significantly associated with esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the DNA methylation-driven genes in ESCC by integrative bioinformatics analysis. METHODS: Data of DNA methylation and transcriptome profiling were downloaded from TCGA database. DNA methylation-driven genes were obtained by methylmix R package. David database and ConsensusPathDB were used to perform gene ontology (GO) analysis and pathway analysis, respectively. Survival R package was used to analyze overall survival analysis of methylation-driven genes. RESULTS: Totally 26 DNA methylation-driven genes were identified by the methylmix, which were enriched in molecular function of DNA binding and transcription factor activity. Then, ABCD1, SLC5A10, SPIN3, ZNF69, and ZNF608 were recognized as significant independent prognostic biomarkers from 26 methylation-driven genes. Additionally, a further integrative survival analysis, which combined methylation and gene expression data, was identified that ABCD1, CCDC8, FBXO17 were significantly associated with patients' survival. Also, multiple aberrant methylation sites were found to be correlated with gene expression. CONCLUSION: In summary, we studied the DNA methylation-driven genes in ESCC by bioinformatics analysis, offering better understand of molecular mechanisms of ESCC and providing potential biomarkers precision treatment and prognosis detection.