Molecular Engineering of a Doubly Quenched Fluorescent Probe Enables Ultrasensitive Detection of Biothiols in Highly Diluted Plasma and High-Fidelity Imaging of Dihydroartemisinin-Induced Ferroptosis.

The occurrence and development of diseases are accompanied by abnormal activity or concentration of biomarkers in cells, tissues, and blood. However, the insufficient sensitivity and accuracy of the available fluorescence probes hinder the precise monitoring of associated indexes in biological systems, which is generally due to the high probe intrinsic fluorescence and false-negative signal caused by the reactive oxygen species (ROS)-induced probe decomposition. To resolve these problems, we have engineered a ROS-stable, meso-carboxylate boron dipyrromethene (BODIPY)-based fluorescent probe, which displays quite a low background fluorescence due to the doubly quenched intrinsic fluorescence by a combined strategy of the photoinduced electron transfer (PET) effect and "ester-to-carboxylate" conversion. The probe achieved a high S/N ratio with ultrasensitivity and good selectivity toward biothiols, endowing its fast detection capability toward the biothiol level in 200×-diluted plasma samples. Using this probe, we achieved remarkable distinguishing of liver injury plasma from normal plasma even at 80× dilution. Moreover, owing to its good stability toward ROS, the probe was successfully employed for high-fidelity imaging of the negative fluctuation of the biothiol level in nonsmall-cell lung cancer (NSCLC) during dihydroartemisinin-induced ferroptosis. This delicate design of suppressing intrinsic fluorescence reveals insights into enhancing the sensitivity and accuracy of fluorescent probes toward the detection and imaging of biomarkers in the occurrence and development of diseases.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Clinical significance and biological function of interferon regulatory factor 1 in non-small cell lung cancer.

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.

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Traditional antibody drug conjugates (ADC) combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells, but there are still many shortcomings in stability, targeting, efficacy, and safety. Novel ADC, such as bi-specific, site-specific, dual-payload, and pro-drug type ADC, can be optimized by simultaneously binding 2 different antigens or epitopes, selecting more stable linkers, coupling with specific amino acid sites of antibodies, carrying different drug payloads, and adopting prodrug strategies, while retaining the characteristics of traditional ADC. Significantly improving the stability, targeting, efficacy and safety of drugs can better meet the needs of clinical treatment. Novel ADC will play a more important role in cancer treatment in the future. Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

The Evaluation of Prognostic Value and Immune Characteristics of Ferroptosis-Related Genes in Lung Squamous Cell Carcinoma.

Background The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). Methods The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. Results Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. Conclusions The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity.

Baseline characteristics and the factors influencing successful smoking cessation: A comparison between a WeChat smoking cessation mini-program and an offline smoking cessation clinic.

INTRODUCTION: Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers' characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC mini-program. METHODS: Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC mini-program (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. RESULTS: The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0-60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). CONCLUSIONS: Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.

Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer.

BACKGROUND: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. METHODS: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39-0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31-0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1-2. CONCLUSIONS: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.

Evaluation of the smoking cessation effects of QuitAction, a smartphone WeChat platform.

INTRODUCTION: Many smokers in China desire to quit, though the success rate among adults is low. This study evaluated the effects of QuitAction, a WeChat smoking cessation platform, summarized the intervention experience of the smoking cessation platform, identified aspects of the platform that necessitated improvement, and provided references for further optimization of the smoking cessation platform. METHODS: This single-arm study was conducted in Hunan, China, from September 2020 to October 2021. Regular smokers, who were aged ≥15 years and willing to quit smoking using QuitAction, were recruited. An in-application questionnaire evaluated participants' baseline smoking status and intention to quit smoking. The QuitAction program included questionnaires regarding the participants' ongoing smoking cessation status at 24 hours, one week, one month and three months after quitting. The smoking cessation procedure was discontinued if the participant had no intention of continuing. The smoking cessation rate, influencing success factors, frequency of use satisfaction, and helpfulness of QuitAction were recorded. RESULTS: A total of 303 participants registered and logged into the QuitAction program, including 59 with incomplete information and 64 with no intention of quitting. The study finally included 180 participants. The smoking cessation rate was 33.9% at 24 hours, 27.2% at one week, 26.1% at one month, and 25.0% at three months. QuitAction was reported as helpful by 94.9% of participants and 95.7% were satisfied with the program. Participants with a quitting difficulty score of 80-100 were less likely to quit smoking than participants with a difficulty score of 0-60 (OR=0.28; 95% CI: 0.10-0.78; p=0.015). Participants using the platform ≥5 times were more likely to quit smoking than those who used the platform <5 times (OR=3.59; 95% CI: 1.51-8.52; p=0.004). CONCLUSIONS: The QuitAction platform provides smoking cessation services that can improve smokers' success rate and improve user experience satisfaction.

Comparison of the baseline characteristics and influencing factors of successful smoking cessation before and during the coronavirus disease pandemic.

INTRODUCTION: Travel and living environment restrictions, which may have positive or negative effects on smoking-related behaviors, were implemented to limit the COVID-19 pandemic. This study aimed to compare the baseline clinical characteristics and smoking cessation (SC) rate at 3 months of patients in an SC clinic in Hunan Province, China before and during the COVID-19 pandemic and identify influencing factors of successful SC. METHODS: Healthy patients at the SC clinic aged ≥18 years before the COVID-19 pandemic and during the COVID-19 pandemic were divided into groups A and B, respectively. The two groups' demographic data and smoking characteristics were compared, and SC interventions were applied by the same medical staff team through telephone follow-up and counselling during the SC procedure. RESULTS: Groups A and B included 306 and 212 patients, respectively, with no significant differences in demographic data. The SC rates of group A (pre COVID-19) and group B (during the COVID-19 pandemic) at 3 months were 23.5% and 30.7%, respectively, after the first SC visit. Those who chose to quit immediately or within 7 days were more successful than those who did not choose a quit date (p=0.002, p=0.000). Patients who learned about the SC clinic via network resources and other methods were more likely to succeed than those who learned about the clinic from their doctor or hospital publications (p=0.064, p=0.050). CONCLUSIONS: Planning to quit smoking immediately or within 7 days of visiting the SC clinic and learning about the SC clinic via the network media or other methods improved the likelihood of successful SC. SC clinics and the harm of tobacco should be promoted via network media. During consultation, the smokers should be encouraged to quit smoking immediately and establish an SC plan, which would help them to quit smoking.

Cognitive behavioral therapy for anxiety and depression in cancer survivors: a meta-analysis.

This study aimed to investigate the effects of cognitive behavioral therapy (CBT) on anxiety and depression in cancer survivors. The PubMed, Embase, PsycINFO, and Cochrane Library databases were searched. Randomized controlled trials that evaluated the effects of CBT in cancer survivors were included. The standardized mean difference (SMD) was used as an effect size indicator. Fifteen studies were included. For the depression score, the pooled results of the random effects model were as follows: pre-treatment versus post-treatment, SMD (95% confidence interval [CI]) = 0.88 (0.46, 1.29), P < 0.001; pre-treatment versus 3-month follow-up, 0.83 (0.09, 1.76), P = 0.08; pre-treatment versus 6-month follow-up, 0.92 (0.27, 1.58), P = 0.006; and pre-treatment versus 12-month follow-up, 0.21 (- 0.28, 0.70), P = 0.40. For the anxiety score, the pooled results of the random effects model were as follows: pre-treatment versus post-treatment, 0.97 (0.58, 1.36), P < 0.001; pre-treatment versus 3-month follow-up, 1.45 (- 0.82, 3.72), P = 0.21; and pre-treatment versus 6-month follow-up, 1.00 (0.17, 1.83), P = 0.02). The pooled result of the fixed effects model for the comparison between pre-treatment and the 12-month follow-up was 0.10 (- 0.16, 0.35; P = 0.45). The subgroup analysis revealed that the geographical location, treatment time and treatment form were not sources of significant heterogeneity. CBT significantly improved the depression and anxiety scores of the cancer survivors; such improvement was maintained until the 6-month follow-up. These findings support recommendations for the use of CBT in survivors of cancer.

Desire for hastened death in advanced cancer: cross-sectional study in China.

OBJECTIVE: To evaluate the incidence of desire for hastened death (DHD) among patients with advanced cancer and to identify factors associated with DHD. METHODS: This was a cross-sectional study of 227 patients with advanced cancer in Hunan Cancer Hospital. The patients were assessed using Chinese version of the Schedule of Attitudes toward Hastened Death, Karnofsky Performance Scale, Quality of Life (QOL), MD Anderson Symptom Inventory and Patient Health Questionnaire Depression Module-9. RESULTS: The number of patients with or without DHD were 71 (31.3%) and 156 (68.7%), respectively. Follow-up visits and average and high QOL were protective factors for DHD; severely disturbed sleep, symptoms that severely interfered with mood, and symptoms that severely interfered with relations with other people were risk factors for DHD. CONCLUSIONS: The incidence of the DHD in patients with advanced cancer at home is high. Those who have low QOL, severely disturbed sleep, symptoms that severely interfered with mood, or symptoms that severely interfered with relations with other people should be paid attention to. These data provide a theoretical basis for the early detection and diagnosis of the desire to accelerate death of patients with advanced cancer.

The psychological impact of COVID-19 pandemic on healthcare workers.

Background: As unprecedented and prolonged crisis, healthcare workers (HCWs) are at high risk of developing psychological disorders. We investigated the psychological impact of COVID-19 pandemic on HCWs. Methods: This cross-sectional study randomly recruited 439 HCWs in Hunan Cancer Hospital via a web-based sampling method from June 1st 2021 to March 31st 2022. Anxiety and depression levels were measured using Hospital Anxiety and Depression Scale (HADS). The Post Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) was used to assess the presence and severity of PTSD. Fear was measured by modified scale of SARS. Data were collected based on these questionnaires. Differences in fear, anxiety, depression and PTSD among HCWs with different clinical characteristics were analyzed using a multivariate analysis of variance. The Cronbach's alpha scores in our samples were calculated to evaluate the internal consistency of HADS, fear scale and PCL-5. Results: The prevalence of anxiety, depression, and PTSD in HCWs was 15.7, 9.6, and 12.8%, respectively. Females and nurses were with higher fear level (P < 0.05) and higher PTSD levels (P < 0.05). Further analysis of female HCWs revealed that PTSD levels in the 35-59 years-old age group were higher than that in other groups; while married female HCWs were with increased fear than single HCWs. The internal consistency was good, with Cronbach's α = 0.88, 0.80 and 0.84 for HADS, fear scale, and PCL, respectively. Conclusion: Gender, marital status, and age are related to different level of psychological disorders in HCWs. Clinical supportive care should be implemented for specific group of HCWs.

The prevalence of psychological disorders among cancer patients during the COVID-19 pandemic: A meta-analysis.

PURPOSE: We aimed to assess the prevalence rate (PR) of depression, anxiety, posttraumatic stress disorder (PTSD), insomnia, distress, and fear of cancer progression/recurrence among patients with cancer during the COVID-19 pandemic. METHODS: Studies that reported the PR of six psychological disorders among cancer patients during the COVID-19 pandemic were searched in PubMed, Embase, PsycINFO, and Web of Science databases, from January 2020 up to 31 January 2022. Meta-analysis results were merged using PR and 95% confidence intervals, and heterogeneity among studies was evaluated using I2 and Cochran's Q test. Publication bias was examined using funnel plots and Egger's tests. All data analyses were performed using Stata14.0 software. RESULTS: Forty studies with 27,590 participants were included. Pooled results showed that the PR of clinically significant depression, anxiety, PTSD, distress, insomnia, and fear of cancer progression/recurrence among cancer patients were 32.5%, 31.3%, 28.2%, 53.9%, 23.2%, and 67.4%, respectively. Subgroup analysis revealed that patients with head and neck cancer had the highest PR of clinically significant depression (74.6%) and anxiety (92.3%) symptoms. Stratified analysis revealed that patients with higher education levels had higher levels of clinically significant depression (37.2%). A higher level of clinically significant PTSD was observed in employed patients (47.4%) or female with cancer (27.9%). CONCLUSION: This meta-analysis evaluated the psychological disorders of cancer patients during the COVID-19 outbreak. Therefore, it is necessary to develop psychological interventions to improve the mental health of cancer patients during the pandemic.

A Novel Risk Score Model of Lactate Metabolism for Predicting over Survival and Immune Signature in Lung Adenocarcinoma.

BACKGROUND: The role of lactate acid in tumor progression was well proved. Recently, it was found that lactate acid accumulation induced an immunosuppressive microenvironment. However, these results were based on a single gene and it was unclear that lactate acid genes were associated with immunotherapy and able to predict overall survival. METHODS: Genes and survival data were acquired from TCGA, GEO and GENECARDS. PCA and TSNE were used to distinguish sample types according to lactate metabolism-associated gene expression. A Wilcox-test examined the expression differences between normal and tumor samples. The distribution in chromatin and mutant levels were displayed by Circo and MAfTools. The lactate metabolism-associated gene were divided into categories by consistent clustering and visualized by Cytoscape. Immune cell infiltration was evaluated by CIBERSORT and LM22 matrix. Enrichment analysis was performed by GSVA. We used the ConsensusClusterPlus package for consistent cluster analysis. A prognostic model was constructed by Univariate Cox regression and Lasso regression analysis. Clinical specimens were detected their expression of genes in model by IHC. RESULTS: Most lactate metabolism-associated gene were significantly differently expressed between normal and tumor samples. There was a strong correlation between the expression of lactate metabolism-associated gene and the abundance of immune cells. We divided them into two clusters (lactate.cluster A,B) with significantly different survival. The two clusters showed a difference in signal, immune cells, immune signatures, chemokines, and clinical features. We identified 162 differential genes from the two clusters, by which the samples were divided into three categories (gene.cluster A,B,C). They also showed a difference in OS and immune infiltration. Finally, a risk score model that was composed of six genes was constructed. There was significant difference in the survival between the high and low risk groups. ROC curves of 1, 3, 5, and 10 years verified the model had good predictive efficiency. Gene expression were correlated with ORR and PFS in patients who received anti-PD-1/L1. CONCLUSION: The lactate metabolism-associated genes in LUAD were significantly associated with OS and immune signatures. The risk scoring model that was constructed by us was able to well identify and predict OS and were related with anti-PD-1/L1 therapy outcome.

Lung cancer distress: screening thermometer meta-analysis.

OBJECTIVES: The distress is associated with the life quality and prognosis of patients with lung cancer. Distress thermometer (DT) has been widely recommended for distress screening. This study was conducted to summarise the positive rate of distress in patients with lung cancer using DT screenings. METHODS: The PubMed, Embase, PsyclNFO and Cochrane Library databases were comprehensively searched to identify all eligible studies published before 31 December 2021. Studies were eligible if they were published in peer-reviewed literature and evaluated distress levels by DT. RESULTS: Ten eligible studies, including a total of 2111 patients, were included in this analysis, and their methodological quality was moderate. The pooled positive rate of distress in patients with lung cancer was 49.04% (95% CI 41.51% to 56.60%). The subgroup analysis revealed that the distress positive rate was significantly different (p<0.05) across North America, Europe and China with values of 53.33% (95% CI 45.22% to 61.37%), 43.81% (95% CI 31.57% to 56.43%) and 38.57% (95% CI 33.89% to 43.41%), respectively. Moreover, the distress positive rate was significantly different between men and women (p<0.05). Additionally, in terms of histological type, clinical tumour, node, metastasis stage, previous treatment and DT threshold, the distress positive rate had no significant differences. No significant publication bias was identified by Begg's funnel plot and Egger's test. CONCLUSIONS: The summarised distress positive rate was high and was significantly different according to gender and region. DT screening should be recommended for routine clinical practice and more attention should be given towards distress management.

Synergistic Effects of Redox Couples and Oxygen Vacancies Improve the Tetracycline Degradation Property of La2NiMnO6.

Improving the e- and h+ separation efficiency and promoting the production of more radicals is the key to improving the degradation efficiency of catalytic degradation of antibiotics. On the other hand, intermediate analysis of antibiotics in the dark adsorption and light irradiation process is very important to clarify the entire antibiotic degradation pathway. Here, the La2NiMnO6 (LNMO) catalyst was prepared by the sol-gel method and the calcination method. By changing the calcination temperature (800, 900, and 1000 °C), the LNMO-based catalysts were successfully formed, abbreviated as L-800, L-900, and L-1000. XPS measurements demonstrated the presence of Mn4+, Mn3+, Mn2+, and oxygen vacancies (OVs) in the LNMO-based catalysts. Analysis of PL, PC, EIS, and TR-PL demonstrated that L-900 had the highest separation efficiency and fastest carrier mobility. The LNMO-based catalysts were used to degrade tetracycline (TC). With the optimized catalyst L-900, the decomposition rate of TC reached 99.57% in 120 min. The entire TC degradation pathway was analyzed according to LC-MS measurements. Radical trap experiments and ESR technology revealed that the synergistic effect of Mn4+/Mn3+, Mn4+/Mn2+, and OVs not only effectively separated e- and h+ but also facilitated the formation of superoxide radicals (•O2-) to accelerate TC degradation. Radicals •OH, h+, and •O2- all contributed to TC deterioration in increasing order of importance. In addition, XPS measurements of the L-900 catalyst before and after use indicated that Mn4+/Mn3+, Mn4+/Mn2+, and OVs were not reactants but mediators of e- and h+. Finally, the mechanism of TC degradation with the LNMO-based catalysts was discussed. This work provided new material for TC degradation in the wastewater.

Neutrophil Extracellular Traps Facilitate A549 Cell Invasion and Migration in a Macrophage-Maintained Inflammatory Microenvironment.

INTRODUCTION: The biological functions of neutrophil extracellular traps (NETs) in tumorigenesis have drawn an increasing amount of attention. This study explored the relationship between NETs and the inflammatory microenvironment in lung cancer cell invasion and metastasis. METHODS: NETs were quantified using myeloperoxidase (MPO-DNA) and immunofluorescence staining. Cytokine levels were measured using ELISA kits. THP-1 and A549 cells were used for in vitro experiments. Transwell and Matrigel assays were used to assess the invasion and migration abilities of the cells. RESULTS: Neutrophil infiltration and NET formation were observed in the lung cancer tissues. Compared with healthy controls, the level of MPO-DNA complexes in lung cancer patients increased remarkably and was positively correlated with peripheral blood neutrophil counts, smoking status, and poor prognosis. Increased circulating NET levels were also positively correlated with the levels of inflammatory cytokines, including IL-1ß, IL-6, IL-18, and TNF-α. Neutrophils isolated from patients with lung cancer are more prone to NET release. NETs can promote the invasion and migration ability of THP-1 and A549 cell in coculture systems, while pretreatment with NET inhibitors can effectively reduce NET-induced invasion and metastasis. The ability of NETs to promote invasion and metastasis is partly dependent on macrophages. CONCLUSION: Taken together, our study demonstrated that NETs facilitate A549 cell invasion and migration in a macrophage-maintained inflammatory microenvironment.

Interferon regulatory factor-1 regulates cisplatin-induced apoptosis and autophagy in A549 lung cancer cells.

This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase 3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase 3 activity were evaluated using commercial kits. Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment-induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer.

Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma.

PURPOSE: The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated. PATIENTS AND METHODS: Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset. RESULTS: Seven m6A-related immune prognostic genes were identified. High expression of PSMD10P1, DIDO1, ABCA5, and CIITA was associated with high survival rates, while that of PRC1, ZWILCH, and ANLN was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217-0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833. CONCLUSION: A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.