PurposeSARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase.MethodsThis was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups.ResultsA history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism.ConclusionCOVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

Intermittent hypoxia (IH) and intermittent transcutaneous electrical stimulation (ITES) might benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of combined IH and ITES in OSA is unknown. In this prospective, randomized, controlled crossover study, normoxia, IH, ITES, and IH&ITES were administered to patients with OSA over four single-night sessions. The primary outcome was difference in OSA severity between the interventions according to apnoea-hypopnea index (AHI) and oxygen desaturation index (ODI). The primary efficacy outcome was response to IH, ITES, IH&ITES defined as a ≥50% reduction in AHI compared with normoxia. Twenty participants (17 male, 3 female) completed the trial. The results showed that median (IQR) AHI decreased from 14.5 (10.8, 17.5) events/h with normoxia to 6.9 (3.9, 14.8) events/h with IH (p=0.020), 5.7 (3.4, 9.1) events/h with ITES (p=0.001), and 3.5 (1.8, 6.4) events/h with IH&ITES (p=0.001). AHI was significantly different between IH and IH&ITES (p=0.042) but not between ITES and IH&ITES (p=0.850). For mild-moderate OSA (n=17), IH, ITES, and IH&ITES had a significant effect on AHI (p=0.013, p=0.001, p=0.001, respectively) compared with normoxia, but there were no differences in post hoc pairwise comparisons between intervention groups. No serious adverse events were observed. In conclusion, IH, ITES, and IH&ITES significantly reduced OSA severity. IH&ITES showed better efficacy in mild-moderate OSA than IH and was comparable to ITES. Our data do not support recommending IH&ITES over ITES for OSA.

Purpose We aimed to analyze the clinical features of COVID-19-associated pulmonary aspergillosis (CAPA) during the SARS-CoV-2 Omicron variant pandemic and to reveal the risk factors for CAPA and death. Methods A retrospective cohort study was conducted on 168 CAPA patients from December 8, 2022 to January 31, 2023. 168 COVID-19 patients without secondary fungal infection during this period were matched 1:1 using propensity score matching as controls. Results The incidence of CAPA was 3.8% (168/4421). Compared with patients without fungal infection, CAPA patients had a higher mortality (43.5% vs. 10.1%, P < 0.001). Patients in the death group ( n = 73) were more likely to be admitted to ICU (91.8% vs. 26.3%, p < 0.001), had a shorter ICU length of hospitalization (10 (IQR, 6 ~ 16.5) days vs. 14 (IQR, 8 ~ 37) days, p = 0.012). Immunocompromised status ( p = 0.023), NLR ≥ 5.7 ( p = 0.004), CRP ≥ 50 mg/L ( p = 0.043), and the number of antibiotics ≥ 3 ( p < 0.001) were all risk factors for CAPA; NLR ≥ 5.7 ( p = 0.009) and the number of antibiotics ≥ 3 ( p = 0.018) were all independent risk factors for death. Conclusions During the Omicron variant pandemic, CAPA increased death and ICU length of hospitalization. The risk factors of CAPA and death obtained from the study can help us further understand the disease characteristics of CAPA and better guide our clinical decision-making.

Background Mycoplasma pneumoniae infections have increased in China recently, causing some evidence of familial clustering. The purpose of this study was to compare the clinical features of parents and children in cases of familial clustering of Mycoplasma pneumoniae infection. Methods A retrospective analysis was performed on the cases of familial clustering of Mycoplasma pneumoniae infection, and the clinical characteristics of parents and children were compared. Results We identified 63 families, of these, 57 (65.5%) adults and 65 (94.2%) children required hospitalization. Fifty-seven adults (mean age 35.1 ± 4.6 years, 80.7% female) and 55 children (mean age 6.3 ± 3.9 years, 54.5% female) were included in the analysis. The incidence of mycoplasma infection in adults had increased gradually over the past year, while the rate in children had spiked sharply since June 2023. The clinical symptoms were similar in the two groups, mainly fever and cough. The peak temperature of children was higher than that of adults (39.1 ± 0.7℃ vs 38.6 ± 0.7℃, p = 0.004). Elevated lactate dehydrogenase was more common in children than in adults (77.8% vs 11.3%, p < 0.001). Bronchial pneumonia and bilateral involvement were more common in children, while adults usually had unilateral involvement. Three (60%) adults and 21 (52.5%) children were macrolide-resistant Mycoplasma pneumoniae infected. Children were more likely to be co-infected (65.5% vs 22.8%, p < .001). Macrolides were used in most children and quinolones were used in most adults. Ten (18.2%) children were diagnosed with severe Mycoplasma pneumoniae pneumonia, whereas all adults had mild disease. Children had a significantly longer fever duration than adults ((5.6 ± 2.2) days vs (4.1 ± 2.2) days, p = 0.002). No patient required mechanical ventilation or died. Conclusions Mycoplasma pneumoniae infection shows a familial clustering epidemic trend at the turn of summer and autumn, with different clinical characteristics between parents and children.

This prospective, randomized, controlled clinical trial assessed the therapeutic effects of major ozone autohemotherapy (O3-MAH) in patients with post-acute sequelae of COVID-19 (PASC). Seventy-three eligible participants were randomly assigned to an O3-MAH plus conventional therapy group (n = 35) or a conventional therapy alone group (n = 38). Symptom score, pulmonary function, 6-minute walk distance (6MWD), and hematological, biochemical, and immunological parameters were evaluated before and after the interventions. Both groups demonstrated improvements in various parameters post-intervention, but efficacy was greater in the O3-MAH group than the conventional treatment group; with intervention effectiveness defined as a ≥ 50 % reduction in symptom score, 25 of 35 patients (71 %) responded to O3-MAH, while 17/38 patients (45 %) responded to conventional treatment alone (P = 0.0325). Significant improvements in symptom scores (P = 0.0478), tidal volume (P = 0.0374), predicted 6MWD (P = 0.0032), and coagulation and inflammatory indicators were noted in the O3-MAH group compared with the conventional treatment group. O3-MAH was more likely to be effective in patients with elevated CRP levels. Furthermore, O3-MAH markedly improved cellular immunity, and this improvement became more pronounced with extended treatment duration. In summary, combining O3-MAH with conventional treatment was more effective than conventional therapy alone in improving symptoms, pulmonary function, inflammation, coagulation, and cellular immunity in patients with PASC. Further research is now warranted to validate these findings and individualize the regimen.

BACKGROUND: In certain situations, masks are worn during sleep to prevent respiratory infections. However, the effects of mask wearing on cardiopulmonary function during sleep are unknown. This study aimed to determine whether wearing masks during sleep has an impact on cardiopulmonary function, including in patients with obstructive sleep apnea. METHODS: This was a prospective, randomized crossover-controlled trial. The effects of wearing surgical masks or N95 respirators on cardiopulmonary function were measured in healthy subjects and patients with mild-moderate obstructive sleep apnea. Sleep breathing parameters were monitored during nocturnal sleep using a sleep monitor, and subjective feelings about mask wearing were assessed using a questionnaire. RESULTS: Wearing masks during sleep at night did not significantly impact sleep breathing parameters. Furthermore, there were no significant differences in heart rate, blood oxygenation, and blood pressure before and after wearing masks. However, wearing masks, especially the N95 mask, had an adverse impact on sleep quality, and masks were found to be subjectively uncomfortable. CONCLUSION: Wearing masks during sleep at night does not adversely affect cardiopulmonary function but they can be uncomfortable, especially the N95 mask. Thus, in circumstances where wearing N95 masks during nocturnal sleep proves intolerable, we recommend the use of surgical masks as a more comfortable alternative. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. center dot The American Journal of Medicine (2024) 137:1128-1135

Obstructive sleep apnea (OSA) incurs a huge individual, societal, and economic burden. Specific and selective targeting of hypoglossal motor neurons could be an effective means to treat OSA. Bioluminescent-optogenetics (BL-OG) is a novel genetic regulatory approach in which luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels, increase neuronal excitability when exposed to a suitable substrate. Here we develop and validate the feasibility of BL-OG for sleep-disordered breathing (SDB). Upon confirming that diet-induced obese mice represent an excellent SDB model, we employed a method of targeting the hypoglossal nucleus (12 N) by peripherally injecting retrogradely transported rAAV2/Retro. With AAV transduction, the eLMO3 protein is expressed in hypoglossal motor neurons (HMN); administration of CTZ results in production of bioluminescence that in turn activates the tethered channelrhodopsin, leading to an increase in the firing of HMN and a 2.7 ± 0.8-fold increase in phasic activity of the genioglossus muscle, a 7.6 ± 1.8-fold increase in tonic activity, and improvements in hypoventilation and apnea index without impacting sleep structure. This is therefore the first study to leverage the rAAV2/Retro vector to execute the BL-OG approach in SDB, which amplified genioglossus muscle discharge activity and increased airflow in mice after activation. This study marks the pioneering utilization of BL-OG in SDB research.

BackgroundCardiac arrhythmias are very common in patients with obstructive sleep apnea (OSA), especially atrial fibrillation (AF) and nonsustained ventricular tachycardia (NVST). Cardiac autonomic dysfunction and structural remodeling caused by OSA provide the milieu for cardiac arrhythmia development. This study aimed to determine whether OSA is associated with various cardiac arrhythmias and investigate potential pathophysiologic pathways between them.MethodsThe analysis covered 600 patients with clinical suspicion of OSA hospitalized in Renmin Hospital of Wuhan University between January 2020 and May 2023. After undergoing sleep apnea monitor, all subjects received laboratory tests, Holter electrocardiography, and Echocardiography.ResultsCompared with those without OSA and adjusting for potential confounders, subjects with moderate OSA had three times the odds of AF (odds ratio [OR] 3.055; 95% confidence interval [CI], 1.002–9.316; p = 0.048). Subjects with severe OSA had three times the odds of AF (OR 3.881; 95% CI, 1.306–11.534; p = 0.015) and NSVT (OR 3.690; 95% CI, 0.809–16.036; p = 0.046). There were significant linear trends for the association between OSA severity with AF and NVST (p < 0.05). And this association was mediated by cardiac structural changes including left atrial diameter, left ventricular diastolic diameter, right atrial diameter and right ventricular diameter. In addition, the ratio of low-frequency and high-frequency individually mediated the association between severe OSA and NVST.ConclusionThis study demonstrated that severe OSA was independently associated with AF and NSVT, and this association was mediated by autonomic nervous system changes and cardiac structural remodeling.

STUDY OBJECTIVESPolycystic ovary syndrome (PCOS) confers a high risk of obstructive sleep apnea (OSA). Here we investigated the effect of OSA on first in vitro fertilization (IVF) cycle metrics and outcomes in PCOS patients.METHODSThis was a prospective cohort study of PCOS patients undergoing first IVF at a single tertiary center between October 1, 2021 and September 30, 2022. Patients were screened for OSA before IVF and grouped accordingly. Clinical and IVF cycle data were compared between groups.RESULTSOSA was found in 37.2% of 156 PCOS patients, with longer infertility duration (4.3±2.5 vs. 3.4±2.0 years) and lower levels of anti-Mullerian and luteinizing hormones than non-OSA patients (6.44±2.96 vs. 8.69±4.03 µg/L and 6.30±5.02 vs. 8.46±6.09 U/L). Antral follicle count was lower in OSA patients (28.9±12.4 vs. 33.2±12.9). During ovarian stimulation, OSA patients required significantly higher doses of gonadotropin (2080.8±1008.7 vs. 1682.8±619.9 U) and had lower peak estradiol level (4473.5±2693.0 vs. 5455.7±2955.1 pmol/L), fewer retrieved oocytes, high-quality and available embryos (17.8±7.2 vs. 21.9±10.5, 4.5±4.4 vs. 6.2±4.6, 5.2±4.3 vs. 7.4±5.0). Eleven patients were excluded for having no embryos or missing transfer. Therefore, we analyzed the outcome of the first embryo transfer in 145 patients. The biochemical and clinical pregnancy rates were lower in OSA than non-OSA patients (51.9% vs 66.7% and 42.3% vs 60.2%). OSA was independently associated with clinical pregnancy rate after controlling for several confounders (p=0.043).CONCLUSIONSOSA impairs female fertility in PCOS patients, suggesting an adverse effect on IVF cycle stimulation characteristics and clinical outcomes.

Background Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. Methods This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). Findings Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. Interpretation IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.

In a prospective, randomized, controlled crossover study, we explored the effects of acute intermittent hypoxia and acute continuous hypoxia on patients with mild-moderate obstructive sleep apnea. Over three single-night sessions, subjects were alternately exposed to normoxia, acute continuous hypoxia and acute intermittent hypoxia before sleep. The apnea-hypopnea index and oxygen desaturation index were used to diagnose obstructive sleep apnea and evaluate efficacy. A responder was defined as a participant with a ≥ 50% reduction in apnea-hypopnea index between normoxia and hypoxia exposure. Sixteen participants with mild-moderate obstructive sleep apnea completed the study. Compared with normoxia, the mean apnea-hypopnea index decreased by 8.9 events per hr (95% confidence interval, 4.2-13.6, p = 0.001) with acute intermittent hypoxia and by 4.1 events per hr (95% confidence interval, 0.5-8.8, p = 0.082) with acute continuous hypoxia, equating to a mean decrease in apnea-hypopnea index of 4.8 events per hr (95% confidence interval, 0.1-9.5, p = 0.046) with acute intermittent hypoxia compared with acute continuous hypoxia. Compared with normoxia, the mean oxygen desaturation index decreased by 9.8 events per hr (95% confidence interval, 4.4-15.1, p = 0.001) with acute intermittent hypoxia but did not significantly decrease with acute continuous hypoxia; the mean oxygen desaturation index decreased by 7.2 events per hr (95% confidence interval, 1.8-12.6, p = 0.010) with acute intermittent hypoxia compared with acute continuous hypoxia. Of the 16 participants, 11 responded to acute intermittent hypoxia and four responded to acute continuous hypoxia (p = 0.032), of whom eight of 11 cases and all four cases had oxygen desaturation indexes <5 events per hr, respectively (p = 0.273). All participants tolerated acute intermittent hypoxia and there were no obvious adverse events during acute intermittent hypoxia exposure. In conclusion, acute intermittent hypoxia exposure improved apnea-hypopnea index and oxygen desaturation index in patients with mild-moderate obstructive sleep apnea, suggesting that further prospective validation of intermittent hypoxia exposure in patients with obstructive sleep apnea is needed to establish its clinical feasibility as a therapeutic modality.

PurposeContinuous transcutaneous electrical stimulation (CTES) of the genioglossus muscle may benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of intermittent transcutaneous electrical stimulation (ITES) for OSA is unclear.MethodsThis was a randomised, controlled, crossover study to compare the effects of ITES and CTES of the genioglossus muscle. Over three single-night sessions, participants were alternately subjected to three genioglossus stimulation modalities during sleep (sham, CTES and ITES). The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) were used for OSA diagnosis and to evaluate efficacy. A responder was defined as an individual with a ≥50% reduction in AHI together with <10 AHI events per hour and/or an ODI reduction of ≥25% between sham stimulation and electrical stimulation nights.ResultsFifteen men with OSA completed the study. Compared with sham, the median AHI with ITES decreased by 13.3 events/hour (95% CI 3.1 to 23.5, p=0.030) and by 7.3 events/hour (95% CI −3.9 to 18.5, p=0.825) with CTES. The median ODI was reduced by 9.25 events/hour (95% CI 0.5 to 18.0) with ITES and 3.3 events/hour (95% CI −5.6 to 12.2) with CTES; however, there was no significant difference between groups. Furthermore, ITES outperformed CTES with respect to longest apnoea duration (median (95% CI), 9.5 (0.0 to 19.0), p=0.011)) and the highest sleep efficiency (12.2 (2.7 to 21.7), p=0.009). Of the 15 participants, 8 responded to ITES and 3 responded to CTES (p=0.058), of whom all eight cases and two out of three cases had ODIs <5 events/hour, respectively. All participants tolerated ITES well.ConclusionsITES improved upper airway obstruction in patients with OSA, suggesting that further prospective validation of the intermittent approach is warranted.Trial registration numberChiCTR2100050138.

Obstructive sleep apnea (OSA) has several notable complications such as hypertension and diabetes. Studies have also shown that OSA is associated with erectile dysfunction and reduced androgen levels. However, the effect of OSA on semen quality remains poorly studied. Men attending a tertiary reproductive center for semen analysis were tested with a portable sleep breathing monitor. Patients were divided into four groups based on their apnea hypopnea index: none, mild, moderate, and severe obstructive sleep apnea. Differences between groups were assessed using χ2, and associations were tested with multiple regression analysis. We included a total of 175 male subjects with a mean age of 32.2 ± 3.6 years. There were significant differences between groups in progressive sperm motility (

Currently, no pharmacotherapy is routinely used for obstructive sleep apnea (OSA). Recently, combined noradrenergic plus antimuscarinic agents have been evaluated for the treatment of OSA in several trials. This systematic review and meta-analysis following PRISMA guidelines investigated the efficacy and safety of this combination drug regimen for the treatment of OSA. Seven databases were systematically screened for randomized controlled trials (RCTs) studying combined noradrenergic plus antimuscarinic agents for OSA to April 2022. Nine RCTs were identified for systematic review and five for meta-analysis. There were significant differences between OSA patients taking noradrenergic plus antimuscarinic agents and placebo with respect to sleep apnea-hypopnea index [mean difference (MD)-11.27 events/h, 95%CI (-21.69,-0.84) events/h; P = 0.03]; nadir oxygen saturation [MD 5.06%, 95% CI (2.57, 7.55)%; P < 0.0001], and arousal index [MD-8.17 events/h, 95% CI (-15.01,-1.33) events/h; P = 0.02] but not sleep efficiency. Our systematic review revealed that drug therapy modestly improved loop gain and upper airway collapsibility but decreased arousal threshold. A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on one night significantly reduced OSA severity and improved OSA upper airway function. The long-term efficacy and safety of drug combinations in OSA patients now require further study. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

While there is emerging evidence that hypoxia critically contributes to the pathobiology of obstructive sleep apnea (OSA), the diagnostic value of measuring hypoxia or its surrogates in OSA remains unclear. Here we investigated the diagnostic value of hypoxia-related genes and explored their potential molecular mechanisms of action in OSA. Expression data from OSA and control subjects were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between OSA and control subjects were identified using the limma R package and their biological functions investigated with the clusterProfiler R package. Hypoxia-related DEGs in OSA were obtained by overlapping DEGs with hypoxia-related genes. The diagnostic value of hypoxia-related DEGs in OSA was evaluated by receiver operating curve (ROC) analysis. Random forest (RF) and lasso machine learning algorithms were used to construct diagnostic models to distinguish OSA from control. Geneset enrichment analysis (GSEA) was performed to explore pathways related to key hypoxia-related genes in OSA. Sixty-three genes associated with hypoxia, transcriptional regulation, and inflammation were identified as differentially expressed between OSA and control samples. By intersecting these with known hypoxia-related genes, 17 hypoxia-related DEGs related to OSA were identified. Protein-protein interaction network analysis showed that 16 hypoxia-related genes interacted, and their diagnostic value was further explored. The 16 hypoxia-related genes accurately predicted OSA with AUCs >0.7. A lasso model constructed using AREG, ATF3, ZFP36, and DUSP1 had a better performance and accuracy in classifying OSA and control samples compared with an RF model as assessed by multiple metrics. Moreover, GSEA revealed that AREG, ATF3, ZFP36, and DUSP1 may regulate OSA via inflammation and contribute to OSA-related cancer risk. Here we constructed a reliable diagnostic model for OSA based on hypoxia-related genes. Furthermore, these transcriptional changes may contribute to the etiology, pathogenesis, and sequelae of OSA.

N6-methyladenosine (m6A) has recently emerged as an important regulatory mechanism for gene expression and aberrant m6A modification plays an important role in tumor progression. Emerging evidence has shown that aberrant m6A modification induced by cigarette smoking is involved in carcinogenesis, but whether cigarette smoking affects m6A modification and thus deteriorates to non-small cell lung cancer (NSCLC) is still unclear. Here, we identified a tumor suppressor gene-DAPK2 which was significantly associated with poor prognosis of NSCLC patients, especially in patients with a smoking history. Low levels of DAPK2 were detected in smokers and in NSCLC tissues. Cigarette smoking induced aberrant N6-methyladenosine modification of DAPK2, which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. Mechanistically, we further demonstrated that DAPK2 functions as a tumor suppressor and downregulation of DAPK2 substantially enhances the proliferation and migration abilities in vitro and in vivo by activating NF-κB signaling pathway. Notably, the BAY 11-7085, a NF-κB signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells. Our study reveals that cigarette smoking induces aberrant N6-methyladenosine of DAPK2 to promote NSCLC progression, which provides new insight into the mechanisms of NSCLC progression and a specific therapeutic target for NSCLC patients with a smoking history.