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.

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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 &gt;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.

ObjectiveTo evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19.MethodsA single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone. The primary endpoint was time to sustained clinical recovery.ResultsFifty-seven participants were randomized into two groups: 27 received leflunomide plus symptomatic treatment and 30 were assigned to symptomatic treatment alone. Participants treated with leflunomide had a shorter fever duration [3.0 interquartile range (IQR, 2.0–4.0) days and 4.0 (IQR, 3.0–6.0) days, respectively (p = 0.027)] and reduced viral shedding [7 (IQR, 6–9.5) days and 9.0 (IQR, 7.5–12.0) days, respectively (p = 0.044)] compared with individuals treated with symptomatic treatment alone. However, there were no significant differences in time to sustained clinical recovery between the two groups [hazard ratio, 1.329 (95% confidence interval, 0.878–2.529); p = 0.207].ConclusionIn acute adult COVID-19 patients presenting within 5 days of symptom onset, leflunomide combined with symptomatic treatment reduced fever duration and viral shedding time.Clinical Trial Registrationhttps://www.chictr.org.cn/about.html, ChiCTR2100051684.

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