Controlling smoking: A smoking epidemic model with different smoking degrees in deterministic and stochastic environments.

Engaging in smoking not only leads to substantial health risks but also imposes considerable financial burdens. To deepen our understanding of the mechanisms behind smoking transmission and to address the tobacco epidemic, we examined a five-dimensional smoking epidemic model that accounts for different degrees of smoking under both deterministic and stochastic conditions. In the deterministic case, we determine the basic reproduction number, analyze the stability of equilibria with and without smoking, and investigate the existence of saddle-node bifurcation. Our analysis reveals that the basic reproduction number cannot completely determine the existence of smoking, and the model possesses bistability, indicating its dynamic is susceptible to interference from environmental noises. In the stochastic case, we establish sufficient conditions for the ergodic stationary distribution and the elimination of smokers by constructing appropriate Lyapunov functions. Numerical simulations suggest that the effects of inevitable random fluctuations in the natural environment on controlling the smoking epidemic may be beneficial, harmful, or negligible, which are closely related to the noise intensities, initial smoking population sizes, and the effective exposure rate of smoking transmission (ß). Given the uncontrollable nature of environmental random effects, effective smoking control strategies can be achieved by: (1) accurate monitoring of initial smoking population sizes, and (2) implementing effective measures to reduce ß. Therefore, it is both effective and feasible to implement a complete set of strong MPOWER measures to control smoking prevalence.

The role of single-cell RNA sequencing in cardiac tumour - a case report.

A 65-year-old woman presented to our hospital with 5 days of chest tightness, dyspnoea, and lower abdominal distension. Echocardiography revealed a mass in the right atrium. An emergency operation was carried out to prevent tumour shedding. The patient was discharged on the 4th day of tumour resection, without any complications At the 18 months follow-up, she suffered from kidney and lung tumours. She refused any treatment and passed away. scRNA-seq was applied to analyse the nature of the tumour. The cellular components of benign tumours include chondrocytes, smooth muscle cells, fibroblasts, mesenchymal stromal cells, and osteoblasts. Additionally, the cyclic guanosine monophosphate (cGMP-PKG) signalling pathway, transcriptional misregulation in cancer, and the p53 signalling pathway may be related to the growth of this tumour. scRNA-seq is a good approach to analyse growth patterns of cardiac tumours and helpful for distinguishing the nature of the tumour.

CircDiaph3 influences PASMC apoptosis by regulating PI3K/AKT/mTOR pathway through IGF1R.

The pathogenesis of pulmonary hypertension has not been elucidated. We investigated the role of a circular ribonucleic acid, circDiaph3, in the proliferation and migration of pulmonary artery smooth muscle cells during pulmonary hypertension. CircDiaph3 overexpression in blood samples of patients with pulmonary hypertension was analyzed by real-time quantitative polymerase chain reaction. Subsequently, a rat model of pulmonary arterial hypertension was established under hypoxic conditions. Pulmonary artery smooth muscle cells were harvested from the rat model for subsequent experiments with small interfering ribonucleic acid-mediated knockdown of circDiaph3. In cell model, we found that PI3K, AKT, mTOR and insulin-like growth factor 1 signaling pathway (IGF1R) and smooth muscle cell marker genes (α-SMA, Vcam1) were significantly downregulated. The overexpression of Igf1r in pulmonary artery smooth muscle cells rescued the downregulated smooth muscle cell genes, IGF1R signaling pathway proteins, increased smooth muscle cell proliferation, and reduced apoptosis. CircDiaph3 regulates the PI3K/AKT/mTOR signaling pathway via IGF1R to inhibit apoptosis and promote proliferation of smooth muscle cells. Additionally, adenovirus-mediated in vivo inhibition of circDiaph3 was carried out in rats with pulmonary arterial hypertension, followed by harvesting of their pulmonary artery smooth muscle cells for subsequent experiments. Excessive proliferation of smooth muscle cells in the pulmonary artery has narrowed the pulmonary artery lumen, thereby causing pulmonary hypertension, and our results suggest that circDiaph3 has important value in the treatment of pulmonary hypertension. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03739-0.

Gliotoxin Induced Ferroptosis by Downregulating SUV39H1 Expression in Esophageal Cancer Cells.

BACKGROUND: Gliotoxin, a secondary metabolite isolated from marine-derived Aspergillus fumigatus, has demonstrated anti-tumor properties in several cancers. Ferroptosis, a recently discovered type of programmed cell death that depends on the accumulation of iron and lipid peroxides, participates in the occurrence and development of various diseases, including cancer. A recent patent, US20200383943, has suggested that the promotion of ferroptosis is a method of cancer treatment. Therefore, the development of drugs that induce ferroptosis in cancer cells would constitute a novel therapeutic approach. OBJECTIVE: Gliotoxin is a natural compound which has exhibited anti-tumor properties in multiple cancers, however, studies of the effect of gliotoxin on esophageal cancer are lacking. Although cancer treatment has shown great progress, including traditional surgery, chemotherapy, radiotherapy, and immunotherapy, the prognosis of esophageal cancer is still poor. Therefore, the development of new treatment approaches for esophageal cancer is necessary. METHODS: The effects of gliotoxin on esophageal cancer cells were determined by functional assays, such as CCK-8, wound healing and transwell assays. We used online tools to predict the target genes of gliotoxin, followed by further verification using Western blotting assays. To assess the role of gliotxin in inducing ferroptosis in esophageal cancer, we detected characteristics associated with ferroptosis including ROS, MDA, GSH and Fe2+. RESULTS: Using online tools SEA and SwissTargetPrediction, we predicted that SUV39H1 was the gliotoxin target gene. Furthermore, in esophageal cancer tissues, SUV39H1 was expressed at higher levels than in normal tissues, while in patients with Esophageal Squamous Cell Carcinoma (ESCC), high expression levels of SUV39H1 indicated a poor prognosis. In vitro, we observed that gliotoxin increased ESCC cell death and inhibited cell migration. We treated ESCC cells with pan-caspase inhibitor Z-VAD-FMK or ferroptosis inhibitors, including Fer-1 and DFO. Our results showed that Fer-1 and DFO reduced the toxic effects of gliotoxin, while Z-VAD-FMK did not. Furthermore, gliotoxin treatment reduced tumor weight and volume in the xenograft tumor mouse model. CONCLUSION: In summary, our findings indicate that gliotoxin downregulated SUV39H1 expression in ESCC cells and induced ferroptosis, suggesting a novel natural therapy for ESSC.

A Novel Inflammation-Based Risk Score Predicts Mortality in Acute Type A Aortic Dissection Surgery: The Additive Anti-inflammatory Action for Aortopathy and Arteriopathy Score.

Objective: To develop an inflammation-based risk stratification tool for operative mortality in patients with acute type A aortic dissection. Methods: Between January 1, 2016 and December 31, 2021, 3124 patients from Beijing Anzhen Hospital were included for derivation, 571 patients from the same hospital were included for internal validation, and 1319 patients from other 12 hospitals were included for external validation. The primary outcome was operative mortality according to the Society of Thoracic Surgeons criteria. Least absolute shrinkage and selection operator regression were used to identify clinical risk factors. A model was developed using different machine learning algorithms. The performance of the model was determined using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves, and Brier score for calibration. The final model (5A score) was tested with respect to the existing clinical scores. Results: Extreme gradient boosting was selected for model training (5A score) using 12 variables for prediction-the ratio of platelet to leukocyte count, creatinine level, age, hemoglobin level, prior cardiac surgery, extent of dissection extension, cerebral perfusion, aortic regurgitation, sex, pericardial effusion, shock, and coronary perfusion-which yields the highest AUC (0.873 [95% confidence interval (CI) 0.845-0.901]). The AUC of 5A score was 0.875 (95% CI 0.814-0.936), 0.845 (95% CI 0.811-0.878), and 0.852 (95% CI 0.821-0.883) in the internal, external, and total cohort, respectively, which outperformed the best existing risk score (German Registry for Acute Type A Aortic Dissection score AUC 0.709 [95% CI 0.669-0.749]). Conclusion: The 5A score is a novel, internally and externally validated inflammation-based tool for risk stratification of patients before surgical repair, potentially advancing individualized treatment. Trial Registration: clinicaltrials.gov Identifier: NCT04918108.

Construction of miRNA-mRNA network and a nomogram model of prognostic analysis for prostate cancer.

Background: Dysregulated genetic factors correlate with carcinoma progression. However, the hub miRNAs-mRNAs related to biochemical recurrence in prostate cancer remain unclear. We aim to identify potential miRNA-mRNA regulatory network and hub genes in prostate cancer. Methods: Datasets of gene expression microarray were downloaded from Gene Expression Omnibus (GEO) database for Robust Rank Aggregation (RRA), targeted gene prediction, gene function and signal pathway enrichment analyses, miRNA-mRNA regulatory network construction, core network screening, as well as validation and survival analysis were carried out by using exogenous data. Results: Prostate cancer-related differentially expressed genes were mostly related to actin filament regulation. Moreover, the cGMP-PKG signaling pathway might play a role in prostate cancer progression. As the core of microRNAs, hsa-miR-106b-5p, hsa-miR-17-5p and hsa-miR-183-5p were matched to hub genes (such as TMEM100, FRMD6, NBL1 and STARD4). The expression levels of hub genes in prostate cancer tissues were significantly lower than normal and closely related to prognosis of patients. The ridge regression model was applied to establish a risk score system. Both risk score and Gleason were used to establish a nomogram. Nomogram predicted the area under the [receiver operating characteristic (ROC)] curve (AUC) of biochemical recurrence at 1-, 3-, and 5-year of 0.713, 0.732 and 0.753, respectively. Conclusions: Hub genes were closely related to prostate cancer development and progression, which might become biomarkers for diagnosis and prognosis. This novel nomogram established could be applied to clinical prediction.

Corrigendum: Hinokiflavone Inhibits Growth of Esophageal Squamous Cancer By Inducing Apoptosis via Regulation of the PI3K/AKT/mTOR Signaling Pathway.

[This corrects the article DOI: 10.3389/fonc.2022.833719.].

Discovering Gene Signature Shared by Prostate Cancer and Neurodegenerative Diseases Based on the Bioinformatics Approach.

Background: Prostate cancer (PCa) is one of the highest frequent malignant tumors with very complicated pathogenesis. Genes of neurodegenerative diseases can influence tumor progression. But its role in the progression of PCa remains unclear. The purpose of the present academic work was to identify significant genes with poor outcome and their underlying mechanism. Methods: The GSE70768, GSE88808, and GSE134051 datasets were downloaded to screen the differentially expressed genes (DEGs). The DEG screening criteria were as follows: P < 0.05 and differential fold change |logFC| ≥ 1. The common DEGs (co-DEGs) of the three datasets were obtained by the Robust Rank Aggregation (RRA) method. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed using R software. Protein-protein interaction (PPI) network analysis was performed for co-DEGs using STRING to screen critical genes. Differential expression and prognosis of key genes were analyzed by the online tool Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The intersection gene between key genes and neurodegenerative genes was identified by constructing a Venn diagram. Results: A total of 263 co-DEGs were identified from the three datasets. GO analysis showed that co-DEGs were mainly involved in muscle contraction and blood circulation regulation. The top ten key genes were ACTG2, APOE, F5, CALD1, MYH11, MYL9, MYLK, TPM1, TPM2, and CALM1. GEPIA2 analysis showed that APOE, MYH11, and MYLK differ dramatically between tumor and normal tissues. These key genes are related to disease-free survival (DFS) in PCa. APOE was the intersection gene between key genes and Alzheimer-related genes. Conclusion: The neurodegenerative gene APOE may be a potential prognostic and diagnostic biomarker for PCa.

A Giant Ascending Aortic Aneurysm Compressed the Left Main Bronchus and Esophagus: A Case Report.

We report a 39-year-old Chinese man with a giant ascending aortic aneurysm that compressed the left main bronchus and esophagus. Cabrol procedure was successfully performed. The symptoms of dry cough, dysphagia, chest tightness, and asthma disappeared. Without any complications, the patient was discharged home.

The MLR, NLR, PLR and D-dimer are associated with clinical outcome in lung cancer patients treated with surgery.

OBJECTIVE: The study objective was to investigate the use of peripheral blood biomarkers as predictors of patient survival. The aim of this study was to identify the baseline peripheral blood biomarkers associated with clinical outcome in patients with early lung cancer (stage I-II) treated with surgery. METHODS: We included and analysed data from 376 patients with early-stage lung cancer who underwent a standard lobectomy. Univariate and multivariate Cox regression analyses were performed on all patients to assess the relationships between progression-free survival (PFS) and overall survival (OS) and the peripheral blood biomarker metrics measured before surgical treatment. The peripheral blood parameters included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer). RESULTS: After univariate Cox regression analysis, low MLR, low NLR, low PLR and low D-dimer values were significantly associated with both better OS and PFS (all p < 0.05). In multivariate Cox regression analysis, a low MLR was significantly and independently associated with both better overall survival and better progression-free survival (both p <0.05). A low D-dimer level was significantly and independently associated with better overall survival (p <0.05). Furthermore, the categorization of patients according to the number of factors with favourable results revealed that those without favourable results had significantly worse outcomes than that of those patients with at least one. CONCLUSION: A baseline signature of low MLR, low NLR, low PLR, and low D-dimer values was associated with a better survival outcome for patients treated with surgery. Patients with more favourable results had better survival outcomes.

Hinokiflavone Inhibits Growth of Esophageal Squamous Cancer By Inducing Apoptosis via Regulation of the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: Globally, esophageal cancer ranks as the seventh most common cancer. Esophageal squamous cell carcinoma (ESCC) is one of its major histological types. ESCC accounts for the vast majority of cases in China, and the mortality rate is high. Cisplatin, the standard adjuvant chemotherapy drug for ESCC, has a modest response rate due to the development of drug resistance. Hinokiflavone (HF) is a natural biflavonoid compound with anti-melanoma activity. However, its anti-tumor effect on ESCC and the underlying mechanisms remain largely unknown. METHODS: The ESCC cell lines KYSE150 and TE14 were used. The cell counting kit-8 assay and flow cytometry analysis, along with colony formation, EdU, wound healing, and Transwell migration assays, were performed to assess cell characteristics (viability, migration, invasion, and apoptosis) following treatment with HF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), western blotting, and molecular docking were used to investigate the pathways potentially modulated by HF. In vivo anti-tumor effects of HF were also investigated using a mouse xenograft model. RESULTS: Our findings revealed that HF inhibited ESCC cell proliferation. Hoechst 33342 staining, annexin V-FITC/PI staining, and western blotting confirmed that HF causes caspase-dependent apoptosis. KEGG pathway enrichment analysis and western blotting indicated that the PI3K/AKT/mTOR pathway played an important role in the process of HF-induced apoptosis. Furthermore, HF effectively impaired the migration and invasion abilities of KYSE150 cells and downregulated the expression of the matrix metalloproteinases (MMP) MMP2 and MMP9. HF inhibited tumor growth and exhibited minimal toxicity in the organs of the KYSE150 xenograft model. CONCLUSION: This is the first study to demonstrate the inhibition of ESCC growth and progression by HF. The underlying mechanism is through blocking the PI3K/AKT/mTOR signaling pathway, thereby inhibiting cell proliferation and inducing apoptosis. HF can be used as a complementary/alternative agent for ESCC therapy.

[Levels of tPSA and fPSA and count of peripheral blood neutrophils in the diagnosis of prostate cancer].

OBJECTIVE: To investigate the value of combined detection of tPSA, fPSA and peripheral blood neutrophil count (Neut#) in the diagnosis of PCa. METHODS: This study included 238 cases of PCa, 328 cases of BPH and 303 normal men as healthy controls present at our hospital for medical or physical examination from August 2018 to December 2021. We detected the levels of serum tPSA and fPSA and Neut# of the subjects, and assessed the value of the combined detection in the diagnosis of PCa using logistic regression analysis, ROC curves, Pearman correlation analysis and nonparametric test. RESULTS: There were significant differences in the tPSA and fPSA levels and Neut# between any two of the PCa, BPH and healthy control groups (P < 0.05). The index N of the combined detection of tPSA, fPSA and Neut# showed an evidently higher diagnostic value than that of any single-item detection. The Gleason scores of the subjects were correlated positively with the tPSA and fPSA levels and index N, with the correlation coefficients of 0.184, 0.245 and 0.166 respectively, P < 0.05), and negatively with the Neut#, with the correlation coefficient of －0.168, P < 0.05). Statistically significant differences were observed in the tPSA and fPSA levels, Neut# and index N in those with different Gleason scores (P < 0.05). CONCLUSION: The combined detection of tPSA, fPSA and Neut# improves the diagnosis of PCa and can be applied clinically as an auxiliary diagnostic method.

Circulating biomarker-based risk stratifications individualize arch repair strategy of acute Type A aortic dissection via the XGBoosting algorithm.

Aims: The incremental usefulness of circulating biomarkers from different pathological pathways for predicting mortality has not been evaluated in acute Type A aortic dissection (ATAAD) patients. We aim to develop a risk prediction model and investigate the impact of arch repair strategy on mortality based on distinct risk stratifications. Methods and results: A total of 3771 ATAAD patients who underwent aortic surgery retrospectively included were randomly divided into training and testing cohorts at a ratio of 7:3 for the development and validation of the risk model based on multiple circulating biomarkers and conventional clinical factors. Extreme gradient boosting was used to generate the risk models. Subgroup analyses were performed by risk stratifications (low vs. middle-high risk) and arch repair strategies (proximal vs. extensive arch repair). Addition of multiple biomarkers to a model with conventional factors fitted an ABC risk model consisting of platelet-leucocyte ratio, mean arterial pressure, albumin, age, creatinine, creatine kinase-MB, haemoglobin, lactate, left ventricular end-diastolic dimension, urea nitrogen, and aspartate aminotransferase, with adequate discrimination ability {area under the receiver operating characteristic curve (AUROC): 0.930 [95% confidence interval (CI) 0.906-0.954] and 0.954, 95% CI (0.930-0.977) in the derivation and validation cohort, respectively}. Compared with proximal arch repair, the extensive repair was associated with similar mortality risk among patients at low risk [odds ratio (OR) 1.838, 95% CI (0.559-6.038); P = 0.316], but associated with higher mortality risk among patients at middle-high risk [OR 2.007, 95% CI (1.460-2.757); P < 0.0001]. Conclusion: In ATAAD patients, the simultaneous addition of circulating biomarkers of inflammatory, cardiac, hepatic, renal, and metabolic abnormalities substantially improved risk stratification and individualized arch repair strategy.

Omega-3 Fatty Acids Supplementation Improve Nutritional Status and Inflammatory Response in Patients With Lung Cancer: A Randomized Clinical Trial.

Background and Aims: Clinical studies have reported positive results with omega-3 supplements in patients with cancer. This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation in improving the nutritional status and inflammatory markers of patients with lung cancer. Methods: In a randomized, double-blind, parallel design trial, 60 patients with lung cancer at nutritional status/risk based on the Nutrition Risk Screening 2002 were randomized to be allocated to two study groups, receiving omega-3 fatty acid supplements [eicosapentaenoic acid (EPA) 1.6 g and docosahexaenoic acid (DHA) 0.8 g] or placebo for 12 weeks. Anthropometric measurements [weight, body mass index (BMI), the circumference of the upper arm, and skinfold thickness of triceps], nutrition-based laboratory indices (hemoglobin, albumin, triglyceride, and cholesterol), and inflammatory markers [C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6)] were measured before and after the intervention as study outcomes. Results: No significant difference between the two study groups was observed regarding basic characteristics and study outcomes. Compared with placebo group, omega-3 fatty acid supplementation group showed significant higher weight (66.71 ± 9.17 vs. 61.33 ± 8.03, p = 0.021), albumin (4.74 ± 0.80 vs. 4.21 ± 0.77, p = 0.013), and triglyceride (130.90 ± 25.17 vs. 119.07 ± 14.44, p = 0.032). Inflammatory markers were significantly reduced in omega-3 group compared to placebo (CRP 1.42 ± 0.63 vs. 3.00 ± 1.05, p = 0.001 and TNF-α 1.92 ± 0.65 vs. 4.24 ± 1.19, p = 0.001). No significant difference was observed between the two study groups regarding changes in BMI, the circumference of the upper arm, skinfold thickness of triceps, triglyceride, cholesterol, and IL-6 (p > 0.05). Conclusions: Omega-3 fatty acid supplementation can improve nutritional status and suppress the systemic inflammatory response in patients with lung cancer. Clinical Trial Registration:www.socialscienceregistry.org, identifier: AEARCTR-0007165.

Metastasis pattern and prognosis in men with esophageal cancer patients: A SEER-based study.

ABSTRACT: Esophageal cancer (EC) is relatively common; at the time of diagnosis, 50% of cases present with distant metastases, and most patients are men. This study aimed to examine and compare the clinicopathological characteristics and metastatic patterns of male EC (MEC) and female EC (FEC). In addition, risk factors associated with MEC prognosis were evaluated.The present study population was extracted from the Surveillance Epidemiology and End Results database. MEC characteristics and factors associated with prognosis were evaluated using descriptive analysis, the Kaplan-Meier method, and the Cox regression model.A total of 12,558 MEC cases were included; among them, 3454 cases had distant organ metastases. Overall, 27.5% of the entire cohort were patients with distant organ metastases. Compared with patients with non-metastatic MEC, patients with metastatic MEC were more likely to be aged ≤60 years, of Black and White race, have a primary lesion in the overlapping esophagus segments, and have a diagnosis of adenocarcinoma of poorly differentiated and undifferentiated grade that was treated with radiotherapy and chemotherapy rather than surgery; moreover, they were also more likely to be married and insured. In addition, patients with MEC were more likely to be aged ≤60 years, White race, and diagnosed with a primary lesion in the lower third of the esophagus and overlapping esophagus segments, and treated without chemotherapy, compared with those with FEC. Patients in the former group were also more likely than those in the latter group to be unmarried and have bone metastasis only and lung metastasis only. Liver, lung, and bone metastases separately, and simultaneous liver and lung metastases were associated with poor survival in MEC patients.Metastatic MEC is associated with clinicopathological characteristics and metastatic patterns different from those associated with non-metastatic MEC and metastatic FEC. Metastatic MEC and FEC patients may have similar prognoses. Distant organ metastasis may be associated with poor prognosis in patients with MEC and FEC.

Hepatic Metastasis in Newly Diagnosed Esophageal Cancer: A Population-Based Study.

BACKGROUND: The hepatic metastasis pattern of esophageal cancer (EC) has not been fully explored. The primary objective of this study was to explore the predictors of esophageal cancer with hepatic metastasis (ECHM) at the time of diagnosis. In addition, we also analyzed the factors affecting ECHM prognosis. METHODS: We used the Surveillance, Epidemiology and End Result (SEER) database to identify ECHM patients at the time of initial diagnosis. The ECHM predictors were identified using multivariate logistic regression. Multivariate Cox regression and competing survival risk analyses were performed to identify factors associated with all-cause mortality and EC-specific mortality of ECHM, respectively. RESULTS: A total of 10,965 eligible EC patients were identified in the SEER database between 2010 and 2016, of which 1,197 were ECHM patients, accounting for 10.9% of the entire cohort. In the whole cohort, eight ECHM predictors (age, primary site, grade, histology type, T staging, N staging, insurance status, and number of extrahepatic metastatic sites) were determined using multivariate logistic regression analysis. Multivariate Cox regression and multivariate competing survival risks models confirmed that the male sex, advanced age, squamous cancer, and multiple extrahepatic metastasis increased the risk of both all-cause and EC-specific mortality, whereas chemotherapy and chemotherapy plus radiotherapy significantly reduced the risk of both. CONCLUSIONS: This study explored population-level predictors of hepatic metastasis at the time of EC diagnosis and analyzed the clinical characteristics affecting the prognosis in ECHM patients. These findings may provide clinicians with a reference for the screening and treatment of hepatic metastasis in EC.

Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma.

We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.

Lung Metastases in Newly Diagnosed Esophageal Cancer: A Population-Based Study.

BACKGROUND: Esophageal cancer is one of the most common cancer types, with its most common distant metastatic site being the lung. Currently, population-based data regarding the proportion and prognosis of patients with esophageal cancer with lung metastases (ECLM) at the time of diagnosis is insufficient. Therefore, we aimed to determine the proportion of patients with ECLM at diagnosis, as well as to investigate the prognostic parameters of ECLM. METHODS: This population-based observational study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2016. Multivariable logistic regression was performed to identify predictors of the presence of ECLM at diagnosis. Multivariable Cox regression and competing risk analysis were used to assess prognostic factors in patients with ECLM. Median survival was estimated using Kaplan-Meier curves. RESULTS: Of 10,965 patients diagnosed with esophageal cancer between 2010 and 2016, 713 (6.50%) presented with initial lung metastasis at diagnosis. Lung metastasis represented 27.15% of all cases with metastatic disease to any distant site. Considering all patients with esophageal cancer, multivariable logistic regression indicated that pathology grade, pathology type, T staging, N staging, race, and number of extrapulmonary metastatic sites were predictive factors for the occurrence of lung metastases at diagnosis. The median survival time of patients with ECLM was 4.0 months. Patients receiving chemotherapy or chemoradiotherapy had the longest median overall survival, 7.0 months. Multivariable Cox regression indicated that age, histology type, T2 staging, number of extrapulmonary metastatic sites, and treatment (chemotherapy, radiotherapy, or chemoradiotherapy) were independent predictors for overall survival (OS). Multivariable competing risk analysis determined that age, number of extrapulmonary metastatic sites, and treatment were independent predictors for esophageal cancer-specific survival (CSS). CONCLUSION: The findings of this study may provide important information for the early diagnosis of ECLM, as well as aid physicians in choosing appropriate treatment regimens for these patients.

Potential role of glucosamine-phosphate N-acetyltransferase 1 in the development of lung adenocarcinoma.

Glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is a key enzyme associated with glucose metabolism and uridine diphosphate-N-acetylglucosamine biosynthesis. Abnormal GNPNAT1 expression might be associated with carcinogenesis. We analyzed multiple lung adenocarcinoma (LUAD) gene expression databases and verified GNPNAT1 higher expression in LUAD tumor tissues than in normal tissues. Moreover, we analyzed the survival relationship between LUAD patients' clinical status and GNPNAT1 expression, and found higher GNPNAT1 expression in LUAD patients with unfavorable prognosis. We built GNPNAT1 gene co-expression networks and further annotated the co-expressed genes' Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and various associated regulatory factors. These co-expression genes' functional networks mainly participate in chromosome segregation, RNA metabolic process, and RNA transport. We analyzed GNPNAT1 genetic alterations and co-occurrence networks, and the functional networks of these genes showed that GNPNAT1 participates in multiple steps of cell cycle transition and in the development of some cancers. We assessed the correlation between GNPNAT1 expression and cancer immune infiltrates and showed that GNPNAT1 expression is correlated with several immune cells, chemokines, and immunomodulators in LUAD. We found that GNPNAT1 correlates with LUAD development and prognosis, laying a foundation for further research, especially in immunotherapy.

A self-calibrating logic system and oxidase-based biosensor using Tb3+-doped carbon dots/DNA conjugates.

Tb3+-doped carbon dots (Tb3+@CDs) were prepared in a facile hydrothermal method by using ammonium citrate as carbon source and Tb3+ as dopant. A 15-bp GT-rich single-strand DNA (ssDNA) was introduced to sensitize Tb3+ via the antenna effect for generating two fluorescence signals (CDs and Tb3+), forming a conjugate of Tb3+@CDs/ssDNA. The ratiometric fluorescence of Tb3+@CDs/ssDNA could be reversibly regulated by Ag+ and Cys, in which the fluorescence peak at 546 nm of Tb3+ could be switched to "On" or "Off" as the signal indicator while the fluorescence peak at 444 nm of CDs remained constant as the build-in reference. The proposed Ag+/Cys-mediated reversible fluorescence changes in Tb3+@CDs/ssDNA was also proven for the design of a self-calibrating ratiometric fluorescence logic system. By integrated with the specific reaction between H2O2 and Cys, Tb3+@CDs/ssDNA was applied for ratiometric fluorescence detection of H2O2. More importantly, the sensing strategy could be further successfully extended to the monitoring of H2O2-produced oxidase-related reactions, such as GOx-biocatalyzed oxidation of glucose (the limit of detection: 0.06 µM) and was well applied in rat serum compared to commercial kits. This work unveiled a novel ratiometric fluorescent design, which is cost-effective, simple to prepare and easy-to-use without chemical modification or fluorescence labeling.