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Background: Light at night (LAN) has become a concern in interdisciplinary research in recent years. This global interdisciplinary study aimed to explore the exposure-lag-response association between LAN exposure and lung cancer incidence. Methods: LAN data were obtained from the Defense Meteorological Satellite Program's Operational Linescan System. Data of lung cancer incidence, socio-demographic index, and smoking prevalence of populations in 201 countries/territories from 1992 to 2018 were collected from the Global Burden of Disease Study. Spearman correlation tests and population-weighted linear regression analysis were used to evaluate the correlation between LAN exposure and lung cancer incidence. A distributed lag nonlinear model (DLNM) was used to assess the exposure-lag effects of LAN exposure on lung cancer incidence. Results: The Spearman correlation coefficients were 0.286-0.355 and the population-weighted linear regression correlation coefficients were 0.361-0.527. After adjustment for socio-demographic index and smoking prevalence, the Spearman correlation coefficients were 0.264-0.357 and the population-weighted linear regression correlation coefficients were 0.346-0.497. In the DLNM, the maximum relative risk was 1.04 (1.02-1.06) at LAN exposure of 8.6 with a 2.6-year lag time. After adjustment for socio-demographic index and smoking prevalence, the maximum relative risk was 1.05 (1.02-1.07) at LAN exposure of 8.6 with a 2.4-year lag time. Conclusion: High LAN exposure was associated with increased lung cancer incidence, and this effect had a specific lag period. Compared with traditional individual-level studies, this group-level study provides a novel paradigm of effective, efficient, and scalable screening for risk factors.
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Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.
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Background: Studying the relationship between strenuous sports or other exercises (SSOE) and lung cancer risk remains underexplored. Traditional observational studies face challenges like confounders and inverse causation. However, Mendelian randomization (MR) provides a promising approach in epidemiology and genetics, using genetic variants as instrumental variables to investigate causal relationships. By leveraging MR, we have scrutinized the causal link between SSOE and lung cancer development. Methods: Twelve single-nucleotide polymorphisms (SNPs) associated with SSOE, as identified in previously published genome-wide association studies, were utilized as instrumental variables in our investigation. Summary genetic data at the individual level were obtained from relevant studies and cancer consortia. The study encompassed a total of 11,348 cases and 15,861 controls. The statistical technique of inverse variance-weighting (IVW), commonly employed in meta-analyses and MR studies, was employed to assess the causal relationship between SSOE and lung cancer risk. Results: The MR risk analysis indicated a causal relationship between SSOE and the incidence of lung cancer, with evidence of a reduced risk for overall lung cancer [odds ratio (OR) =0.129; 95% confidence interval (CI): 0.021-0.779; P=0.03], lung adenocarcinoma (OR =0.161; 95% CI: 0.012-2.102; P=0.16) and squamous cell lung cancer (OR =0.045; 95% CI: 0.003-0.677; P=0.03). The combined OR for lung cancer from SSOE (controlling for waist circumference and smoking status) was 0.054 (95% CI: 0.010-0.302, P<0.001). Conclusions: Our MR analysis findings indicate a potential correlation between SSOE and a protective effect against lung cancer development. Further investigation is imperative to uncover the precise mechanistic link between them.
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Exciton-polaritons, which are bosonic quasiparticles with an extremely low mass, play a key role in understanding macroscopic quantum effects related to Bose-Einstein condensation (BEC) in solid-state systems. The study of trapped polaritons in a potential well provides an ideal platform for manipulating polariton condensates, enabling polariton lasing with specific formation in k-space. Here, we realize quantized microcavity polariton lasing in simple harmonic oscillator (SHO) states based on spatial localized excitons in InGaN/GaN quantum wells (QWs). Benefiting from the high exciton binding energy (90 meV) and large oscillator strength of the localized exciton, room-temperature (RT) polaritons with large Rabi splitting (61 meV) are obtained in a strongly coupled microcavity. The manipulation of polariton condensates is performed through a parabolic potential well created by optical pump control. Under the confinement situation, trapped polaritons are controlled to be distributed in the selected quantized energy sublevels of the SHO state. The maximum energy spacing of 11.3 meV is observed in the SHO sublevels, indicating the robust polariton trapping of the parabolic potential well. Coherent quantized polariton lasing is achieved in the ground state of the SHO state and the coherence property of the lasing is analyzed through the measurements of spatial interference patterns and g(2)(τ). Our results offer a feasible route to explore the manipulation of macroscopic quantum coherent states and to fabricate novel polariton devices towards room-temperature operations.
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PURPOSE: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. METHODS: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan-Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. RESULTS: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). CONCLUSION: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Estudos de Coortes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso de 80 Anos ou mais , Adulto , Fluordesoxiglucose F18RESUMO
Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon's optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3-5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders' cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptor de Morte Celular Programada 1/genética , Antígeno CTLA-4/uso terapêutico , Linfócitos T CD8-Positivos , Fator de Crescimento Epidérmico , Tomografia Computadorizada por Raios X , Pulmão/patologia , Receptores de Antígenos de Linfócitos T , CitocinasRESUMO
Background: Malignant esophageal stent esophagorespiratory fistula (ERF) is an abnormal communication between esophagus and airway among advanced tumor patients with indwelling esophageal stent, which is devastating and life-threatening. This study aims to provide a new feasible treatment scheme for malignant esophageal stent ERF and report its potential advantage compared with double stenting, which was recommended by European Society of Gastrointestinal Endoscopy Guideline. Methods: We retrospectively analyzed the medical data of malignant esophageal stent ERF patients between January 2018 to May 2023 at the First Affiliated Hospital of Guangzhou Medical University and divided them into two groups. Group 1 consisted of patients treated with rigid bronchoscopy to remove the esophageal stent and implant Y silicone trachea stent, while group 2 consisted of patients treated with additional airway stenting without removing the esophageal stent. Demographic parameters, disease diagnoses and treatment, radiological findings before and after the intervention, and complications caused by the stents were obtained and analyzed with chi-squared, Mann-Whitney U, independent-samples t-tests, Kaplan-Meier methods, and log-rank test. Results: Ten patients (seven patients in group 1 and three in group 2) were included. No procedure complications occurred in both groups. The mean Karnofsky Performance Score after the procedure significantly improved compared to the pre-procedure (57.14 vs. 77.14, P=0.001) in group 1, while decreased in group 2 (50 vs. 40, P=0.026). The control of pneumonia in group 1 patients is better than that in group 2. There was significant improvement in the degree of dysphagia after the procedure (3.86 vs. 2.43, P=0.002) in group 1, while no improvement was found in group 2 (4.00 vs. 3.33, P=0.423). The mean survival of group 1 was significantly longer group 2 (381.00 vs. 80.33 days, P<0.001, log-rank test). No patient needed stent repositioning due to migration in both groups. Cause of death in the group 1 included disease progression, novel coronavirus pneumonia, massive hemoptysis, and respiratory insufficiency, while group 2 included severe pneumonia and disease progression. No death was directly attributed to the procedure in both groups. Conclusions: Removing the esophageal stent and implanting Y silicone trachea stent through a rigid bronchoscopy is a safe and feasible treatment for malignant esophageal stent ERF. This procedure can effectively seal the fistula, prevent from recurrent aspiration pneumonia, improve the quality of life, and prolong the survival time.
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BACKGROUNDS: Spontaneous ventilation-video-assisted thoracoscopic surgery (SV-VATS) has been applied to non-small cell lung cancer (NSCLC) patients in many centers. Since it remains a new and challenging surgical technique, only selected patients can be performed SV-VATS. We aim to conduct a retrospective single-center study to develop a clinical decision-making model to make surgery decision between SV-VATS and MV (mechanical ventilation) -VATS in NSCLC patients more objectively and individually. METHODS: Four thousand three hundred sixty-eight NSCLC patients undergoing SV-VATS or MV-VATS in the department of thoracic surgery between 2011 and 2018 were included. Univariate and multivariate regression analysis were used to identify potential factors influencing the surgical decisions. Factors with statistical significance were selected for constructing the Surgical Decision-making Scoring (SDS) model. The performance of the model was validated by area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: The Surgical Decision-making Scoring (SDS) model was built guided by the clinical judgment and statistically significant results of univariate and multivariate regression analyses of potential predictors, including smoking status (p = 0.03), BMI (p < 0.001), ACCI (p = 0.04), T stage (p < 0.001), N stage (p < 0.001), ASA grade (p < 0.001) and surgical technique (p < 0.001). The AUC of the training group and the testing group were 0.72 and 0.70, respectively. The calibration curves and the DCA curve revealed that the SDS model has a desired performance in predicting the surgical decision. CONCLUSIONS: This SDS model is the first clinical decision-making model developed for an individual NSCLC patient to make decision between SV-VATS and MV-VATS.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Respiração Artificial , Estudos Retrospectivos , Cirurgia Torácica VídeoassistidaRESUMO
Background: Esophageal cancer is one of the leading causes of cancer death worldwide. A deeper understanding of the trends in annual incidence, mortality, and disability-adjusted life-years (DALYs) of esophageal cancer is critical for management and prevention. In this study, we report on the disease burden of esophageal cancer in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI). Methods: Data on incidence, mortality, and DALYs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The estimated numbers and age-standardized rates for esophageal cancer in 2019 are presented in this paper, as well as trends from 1990 to 2019. All estimates are presented as counts and age-standardized rates per 100,000 population, with 95% uncertainty intervals (UIs) for each estimate. Results: In 2019, nearly 535,000 (95% UI: 467,000-595,000) new cases of esophageal cancer occurred globally. Esophageal cancer was responsible for more than 498,000 (95% UI: 438,000-551,000) deaths and 11.7 million (95% UI: 10.4-12.9 million) DALYs. Worldwide age-standardized rates of esophageal cancer, including incidence, deaths, and DALYs, have declined since 1990. However, the trends differ across countries and territories. Notably, there was a nonlinear but generally inverse correlation between age-standardized DALY rates and SDI. Higher age-standardized incidence and death rates were observed in males compared to females, and both increased with age. Regarding risk factors, smoking, alcohol use, and high body-mass index were 3 predominant contributors to esophageal cancer DALYs in 2019 for both sexes worldwide. Conclusions: This study found a global reduction in the esophageal cancer burden, but substantial heterogeneity remains across regions and countries. Hence, the identification of high-risk groups and the exploration of specific local strategies and primary prevention efforts are required.
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With the progress of wide bandgap semiconductors, compact solid-state light-emitting devices for the ultraviolet wavelength region are of considerable technological interest as alternatives to conventional ultraviolet lamps in recent years. Here, the potential of aluminum nitride (AlN) as an ultraviolet luminescent material was studied. An ultraviolet light-emitting device, equipped with a carbon nanotube (CNT) array as the field-emission excitation source and AlN thin film as cathodoluminescent material, was fabricated. In operation, square high-voltage pulses with a 100 Hz repetition frequency and a 10% duty ratio were applied to the anode. The output spectra reveal a dominant ultraviolet emission at 330 nm with a short-wavelength shoulder at 285 nm, which increases with the anode driving voltage. This work has explored the potential of AlN thin film as a cathodoluminescent material and provides a platform for investigating other ultrawide bandgap (UWBG) semiconductors. Furthermore, while using AlN thin film and a carbon nanotube array as electrodes, this ultraviolet cathodoluminescent device can be more compact and versatile than conventional lamps. It is anticipated to be useful in a variety of applications such as photochemistry, biotechnology and optoelectronics devices.
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INTRODUCTION: A comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies was performed to map the different risk factors and assess the causality for lung cancer. METHODS: Systematic reviews and meta-analyses of observational and interventional studies were reviewed based on PubMed, Embase, Web of Science, and Cochrane Library. Mendelian randomization analyses were conducted to validate the causal associations of those various exposures with lung cancer using summary statistics from 10 genome-wide association studies (GWAS) consortia and other GWAS databases in MR-Base platform. RESULTS: In the review of meta-analyses, 105 risk factors associated with lung cancer were identified from 93 articles. It was found that 72 risk factors were nominally significant (P < 0.05) associated with lung cancer. Mendelian randomization analyses were performed to analyze 36 exposures based on 551 SNPs and 4,944,052 individuals, finding that 3 exposures had a consistent risk/protective effect on lung cancer with the results of the meta-analysis. In Mendelian randomization anaylses, smoking (OR 1.44, 95% CI 1.18-1.75; P = 0.001) and blood copper (OR 1.14, 95% CI 1.01-1.29; P = 0.039) significantly associated with increased risk of lung cancer, whereas aspirin use (OR 0.67, 95% CI 0.50-0.89; P = 0.006) showed protective effects. CONCLUSION: This study mapped putative associations of risk factors for lung cancer, revealing the causal hazard effect of smoking, blood copper, and the protective effect of aspirin use in the development of lung cancer. CLINICAL TRIAL REGISTRY: This study is registered with PROSPERO (CRD42020159082).
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Neoplasias Pulmonares , Fumar , Humanos , Cobre , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Metanálise como AssuntoRESUMO
Background: Respiratory cancer is the leading cause of cancer-related deaths worldwide, but its statistics vary between the East and West. This study aimed to estimate the burdens of tracheal, bronchus, and lung (TBL) cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia, and at regional and national levels. Methods: This research evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) for respiratory tract cancers using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database. Age-standardized rates were calculated for TBL cancer from 1990 to 2019, adjusted for smoking and socio-demographic index (SDI). Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian countries. Results: The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019, while the incidence rate of larynx cancer increased. Smoking was the leading specific risk factor for deaths from both TBL and larynx cancers. The burden of TBL cancer in Asian countries was influenced by SDI and smoking, particularly among males in Central Asia. Deaths, DALYs, and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years, but showed slight downward trends in males and both sexes combined, and an upward trend in females in recent years. Conclusions: The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in Asia. SDI and smoking were the main factors influencing the disease burden of TBL cancer in Asian countries. This study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.
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Background: Low educational attainment has been reported as a risk factor for many diseases. However, conclusion on the association between educational attainment and endometrial cancer (EC) are inconsistent in previous observational studies. This study aims to explore the potential causal association between educational attainment and EC. Methods: A Mendelian Randomization analysis was performed using publicly summary-level data sets of genome-wide association studies (GWAS). A total of 306 single-nucleotide polymorphisms (SNPs) were extracted as instrumental variables for the exposure of educational attainment from the Social Science Genetic Association Consortium GWAS summary data of 1,131,881 participants of European ancestry. SNPs of EC were obtained from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium and the UK Biobank involving 121,885 people. We conducted inverse variance weighted (IVW) to estimate the causal effect as our primary outcome. And we perform several sensitivity analyses, including MR-Egger regression, weighted median method, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier) global test, and leave-one-out sensitivity analysis, to evaluate the effect of pleiotropism on the causal estimates. Results: Genetic predisposition towards 4.2 years of additional educational attainment was associated with 38% lower risk of EC. (odds ratio 0.72, 95% confidence interval 0.62 to 0.83; p = 1.65*10-5). The consistent results of sensitivity analyses indicated our causal estimates were reliable. Genetic predisposition towards longer educational attainment was associated with lower risk of obesity, high waist-to-hip ratio (WHR), and diabetes. Conclusion: This study indicated that low educational attainment was a causal risk factor for EC, especially for EC with endometrioid histology. Low educational attainment might lead to EC through the mediator of obesity, high WHR, and diabetes.
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Importance: A considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking. Objective: To provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer. Data Sources: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022. Study Selection: Published phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic >50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022. Main Outcomes and Measures: Pathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types. Results: A total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma. Conclusions and Relevance: This study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.
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Adenocarcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Neoplasias Esofágicas/tratamento farmacológico , ImunoterapiaRESUMO
Background: Previous studies have shown that metabolites play important roles in phenotypic regulation, but the causal link between metabolites and tumors has not been examined adequately. Herein, we investigate the causality between metabolites and various cancers through a Mendelian randomization (MR) study. Methods: We carried out a two-sample MR analysis based on genetic instrumental variables as proxies for 486 selected human serum metabolites to evaluate the causal effects of genetically determined metabotypes (GDMs) on cancers. Summary data from various cancer types obtained from large consortia. Inverse variance weighted (IVW), MR-Egger and weighted-median methods were implemented to infer the causal effects, moreover, we particularly explored the presentence of horizontal pleiotropy through MR-Egger regression and MR-PRESSO Global test. Metabolic pathways analysis and subgroup analyses were further explored using available data. Statistical analyses were all performed in R. Results: In MR analysis, 202 significant causative relationship features were identified. 7-alpha-hydroxy-3-oxo-4-cholestenoate (ORIVW =1.45; 95% CI: 1.06-1.97; PIVW =0.018), gamma-glutamylisoleucine (ORIVW =1.40; 95% CI: 1.16-1.69; PIVW =0.0004), 1-oleoylglycerophosphocholine (ORIVW =1.22; 95% CI: 1.1-1.35; PIVW =0.0001), gamma-glutamylleucine (ORIVW =4.74; 95% CI: 1.18-18.93; PIVW =0.027) were the most dangerous metabolites for lung cancer, ovarian cancer, breast cancer, and glioma, respectively; while pseudouridine (ORIVW =0.50; 95% CI: 0.30-0.83; PIVW =0.007), 2-methylbutyroylcarnitine (ORIVW =0.77; 95% CI: 0.68-0.86; PIVW =2.9×10-6), 2-methylbutyroylcarnitine (ORIVW =0.77; 95% CI: 0.70-0.85; PIVW =3.4×10-7), glycylvaline (ORIVW =0.13; 95% CI: 0.02-0.75; PIVW =0.021) were associated with lower risk of lung cancer, ovarian cancer, breast cancer, and glioma, respectively. Interestingly, 2-methylbutyroylcarnitine was also associated with decreased risk of lung cancer (ORIVW =0.59; 0.50-0.70; P IVW =1.98×10-9) expect ovarian cancer and breast cancer. In subgroup analysis, 2-methylbutyroylcarnitine was associated with decreased risk of estrogen receptor (ER) positive breast cancer (ORIVW =0.72; 0.64-0.80; PIVW =3.55×10-9), lung adenocarcinoma (LAC) (ORIVW =0.60; 0.48-0.70; PIVW =1.14×10-5). Metabolic pathways analysis identified 4 significant pathways. Conclusions: Our study integrated metabolomics and genomics to explore the risk factors involved in the development of cancers. It is worth exploring whether metabolites with causality can be used as biomarkers to distinguish patients at high risk of cancer in clinical practice. More detailed studies are needed to clarify the mechanistic pathways.
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Background: Family socioeconomic position (SEP) in childhood is an important factor to predict some chronic diseases. However, the association between family SEP in childhood and the risk of lung cancer is not clear. Methods: A systematic search was performed to explore their relationship. We selected education level, socioeconomic positions of parents and childhood housing conditions to represent an individual family SEP. Hazard ratios (HRs) of lung cancer specific-mortality were synthesized using a random effects model. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SEP to assess the possible causal relationship of SEP and risk of lung cancer. Results: Through meta-analysis of 13 studies, we observed that to compared with the better SEP, the poorer SEP in the childhood was associated with the increased lung cancer risk in the adulthood (HR: 1.25, 95% CI: 1.10 to 1.43). In addition, the dose-response analysis revealed a positive correlation between the poorer SEP and increased lung cancer risk. Same conclusion was reached in MR [(education level) OR 0.50, 95% CI: 0.39 to 0.63; P < 0.001]. Conclusion: This study indicates that poor family socioeconomic position in childhood is causally correlated with lung cancer risk in adulthood. Systematic Review Registration: identifier: 159082.
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Neoplasias Pulmonares , Análise da Randomização Mendeliana , Adulto , Escolaridade , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/epidemiologia , Fatores de RiscoRESUMO
Nonlinear multiphoton absorption (MPA) upconversion lasers have critical applications in fluorescence imaging probes and biological photonics. Here, we report the realization of ultralow-threshold six-photon-excited upconversion lasing through cavity quantum electrodynamics effects in a plasmonic microcavity. The value of the Purcell factor (Fp) in hybrid whisper-gallery mode (WGM) is enhanced five-fold relative to a bare microwire (MW), which enhances the nonlinear light-matter interactions dramatically. Compared with a MW, the threshold of six-photon upconversion WGM lasing is reduced by one order magnitude due to plasmonic enhancement effects. In addition, the temperature and polarization characteristics of upconversion lasing via a plasmonic-WGM approach show a distinct evolution, different from a bare MW. This work paves the way for extreme nonlinear optics, taking advantage of the processability and high Purcell factor of plasmonic microcavities.
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Objective: The goal of this study was to explore the feasibility and safety of spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) for non-small-cell lung cancer (NSCLC) patients with poor lung function. Methods: NSCLC patients with poor lung function who underwent SV-VATS or mechanical ventilation VATS (MV-VATS) from 2011 to 2018 were analyzed. 1:2 Propensity score matching (PSM) was applied, and the short- and long-term outcomes between the SV-VATS group and the MV-VATS group were compared. Results: Anesthesia time (226.18 ± 64.89 min vs. 248.27 ± 76.07 min; P = 0.03), operative time (140.85 ± 76.07 min vs. 163.12 ± 69.37 min; P = 0.01), days of postoperative hospitalization (7.29 ± 3.35 days vs. 8.40 ± 7.89 days; P = 0.04), and days of chest tube use (4.15 ± 2.89 days vs. 5.15 ± 3.54 days; P = 0.01), the number of N1 station lymph node dissection (2.94 ± 3.24 vs. 4.34 ± 4.15; P = 0.005) and systemic immune-inflammation index (3855.43 ± 3618.61 vs. 2908.11 ± 2933.89; P = 0.04) were lower in SV-VATS group. Overall survival and disease-free survival were not significantly different between the two groups (OS: HR 0.66, 95% CI: 0.41-1.07, P = 0.09; DFS: HR 0.78, 95% CI: 0.42-1.45, P = 0.43). Conclusions: Comparable short-term and long-term outcomes indicated that SV-VATS is a feasible and safe method and might be an alternative to MV-VATS when managing NSCLC patients with poor lung function.
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BACKGROUND: Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer. METHODS: A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable. RESULTS: In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500-0.740; p < 0.001] with significant heterogeneity (I2 = 83.3%; p < 0.001). However, MR analysis did not sustain the link between genetically-predicted schizophrenia and prostate cancer [odds ratio (OR) 1.033; 95% CI 0.998-1.069; p = 0.065]. The result was robust against extensive sensitivity analyses. CONCLUSIONS: Our study indicated a decreased risk of prostate cancer in schizophrenia patients through meta-analysis, while MR analysis did not support the connection between schizophrenia and prostate cancer. Due to the interaction of genetic variants between binary exposures, we need to be cautious in interpreting and presenting causal associations. Moreover, further research is needed to investigate underlying factors that might link schizophrenia to the risk of prostate cancer.
Assuntos
Neoplasias da Próstata , Esquizofrenia , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Fatores de Risco , Esquizofrenia/epidemiologia , Esquizofrenia/genéticaRESUMO
BACKGROUND: Gastric cancer (GC) is a globally important disease. It is the 5th most common malignancy and the 4th most common cause of death from cancer in the world. Patients with GC are often at an advanced stage when they are first diagnosed, and their overall prognosis is poor due to locally advanced and distant metastasis. This study sought to establish a predictive model of GC distant metastasis and survival that can be used to guide individualized treatment. METHODS: Patients diagnosed with GC from the Surveillance, Epidemiology, and End Results database were enrolled in the study. Univariate and multivariate logistic regression analyses were used to identify risk and prognostic factors for GC patients with distant metastasis. The factors were then used to construct nomograms to predict the probability of distant metastasis and the survival time of GC patients. Receiver operating characteristic (ROC) curve and decision curve analyses were used to verify the prediction ability of the nomograms. RESULTS: We established a comprehensive nomogram to predict the survival time of GC patients and 4 nomograms to predict distant metastasis. Nomograms could help oncologists to formulate treatment strategies and provide hospice care under an overall management model. CONCLUSIONS: Establishing a prediction model for distant metastasis and the survival of GC patients is of great clinical significance. The prediction of distant metastasis could help clinicians to make individualized assessments of patients and formulate individualized examination measures. Survival prediction models could help oncologists to formulate good treatment strategies and provide hospice care.