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Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3' untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF.
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Displasia Broncopulmonar/metabolismo , MicroARNs/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , MicroARNs/genética , MicroARNs/fisiología , Ratas , Ratas Sprague-Dawley , Transfección , Regulación hacia ArribaRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease in preterm infants. Circular RNAs (circRNAs) are key regulators of various biological processes. The present study aimed to explore the biological roles of circRNAs in BPD pathogenesis. METHODS: A newborn BPD rat model was developed to construct a circRNA library; Illumina deep sequencing (Illumina, San Diego, CA, USA) was used to reveal differential expression of circRNAs in the hyperoxia-induced BPD rat models. Sanger sequencing and a reverse transcription-polymerase chain reaction were performed to confirm circRNAs that may be related to BPD. After miRNA binding-site prediction, we constructed a network diagram of circRNA-competing endogenous RNAs (ceRNAs) related to transforming growth factor (TGF)-ß and p53 pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: In total, 256 differentially expressed circRNAs were detected between the hyperoxia group and the normoxia group. Of these circRNAs, 195 were up-regulated and 61 were down-regulated. The differences of circRNA distribution between the two groups were analyzed and six circRNAs were validated in the tissue samples. GO analysis indicated that 6519 target genes were enriched in cell location and biological processes. KEGG pathway enrichment analysis showed that circRNAs involved in 242 KEGG pathways. A network diagram of circRNA-ceRNA related to TGF-ß and p53 pathways was constructed. CONCLUSIONS: CircRNAs are differentially expressed between the BPD model and control group. Many target genes of circRNAs are involved in the developmental process, which suggests that BPD may be associated with pathways including extracellular matrix-receptor interaction, vascular endothelial growth factor signaling and vascular smooth muscle contraction.
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Displasia Broncopulmonar/metabolismo , Regulación de la Expresión Génica/genética , Hiperoxia/metabolismo , ARN Circular/metabolismo , Animales , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patología , Biología Computacional , Modelos Animales de Enfermedad , Regulación hacia Abajo , Perfilación de la Expresión Génica , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hiperoxia/genética , Inmunohistoquímica , Recién Nacido , Pulmón/citología , Pulmón/metabolismo , Pulmón/patología , ARN Circular/genética , Ratas , Ratas Sprague-Dawley , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia ArribaRESUMEN
PURPOSE: To examine surgery performed for obstructive sleep apnea (OSA) in children with syndromic or neurologic comorbidities. MATERIAL AND METHODS: Medical records of 375 children with OSA were retrospectively reviewed, including 142 patients with trisomy 21, 105 with cerebral palsy, 53 with muscular dystrophy, 32 with spinal muscular atrophy, 18 with mucopolysaccharidoses, 14 with achondroplasia, and 11 with Prader-Willi. OUTCOME MEASURES: Apnea-hypopnea index (AHI), complications, length of postoperative stay, and endoscopic findings. RESULTS: 228 patients received 297 surgical interventions, with the remainder undergoing observation or positive pressure ventilation. Adenoidectomy was the most common procedure performed (92.1% of patients), followed by tonsillectomy (91.6%). Average AHI decreased following tonsillectomy, from 12.4 to 5.7 (p = 0.002). The most common DISE finding was the tongue base causing epiglottic retroflexion. Lingual tonsillectomy also resulted in an insignificant decrease in the AHI. CONCLUSIONS: Adenotonsillectomy, when there is hypertrophy, remains the mainstay of management of syndromic and neurologically-impaired children with OSA. However, additional interventions are often required, due to incomplete resolution of the OSA. DISE is valuable in identifying remaining sites of obstruction and guiding future management.
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Adenoidectomía/métodos , Tonsila Faríngea/cirugía , Endoscopía/métodos , Hipnóticos y Sedantes , Enfermedades del Sistema Nervioso/epidemiología , Tonsila Palatina/cirugía , Apnea Obstructiva del Sueño/cirugía , Tonsilectomía/métodos , Tonsila Faríngea/patología , Niño , Comorbilidad , Femenino , Humanos , Hipertrofia , Masculino , Tonsila Palatina/patología , Estudios Retrospectivos , Apnea Obstructiva del Sueño/epidemiologíaRESUMEN
OBJECTIVE: To compare the accuracy and generalizability of an automated deep neural network and the Philip Sleepware G3™ Somnolyzer system (Somnolyzer) for sleep stage scoring using American Academy of Sleep Medicine (AASM) guidelines. METHODS: Sleep recordings from 104 participants were analyzed by a convolutional neural network (CNN), the Somnolyzer and skillful technicians. Evaluation metrics were derived for different combinations of sleep stages. A further comparison between the Somnolyzer and the CNN model using a single-channel signal as input was also performed. Sleep recordings from 263 participants with a lower prevalence of OSA served as a cross-validation dataset to validate the generalizability of the CNN model. RESULTS: The overall agreement between automated and manual scoring for sleep staging in 104 participants outperformed that of the Somnolyzer according to various metrics (accuracy: 81.81 % vs. 77.07 %; F1: 76.36 % vs. 73.80 %; Cohen's kappa: 0.7403 vs. 0.6848). The results showed that the left electrooculography (EOG) single-channel model had minor advantages over the Somnolyzer. In terms of consistency with manual sleep staging, the CNN model demonstrated superior performance in identifying more pronounced sleep transitions, particularly in the N2 stage and sleep latency metrics. Conversely, the Somnolyzer showed enhanced proficiency in the analysis of REM stages, notably in measuring REM latency. The accuracy in the cross-validation set of 263 participants was also above 80 %. CONCLUSIONS: The CNN-based automated deep neural network outperformed the Somnolyzer and is sufficiently accurate for sleep study analyses using the AASM classification criteria.
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Redes Neurales de la Computación , Polisomnografía , Fases del Sueño , Humanos , Fases del Sueño/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polisomnografía/métodos , Anciano , Electrooculografía/métodos , Procesamiento de Señales Asistido por ComputadorRESUMEN
Objective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference. Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA. Results: The OWSA-REI (26.5±18.5 events/h) correlated well with PSG-AHI (33.2±25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: -6.7, 95% CI:16.0 to -29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values. Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for smartwatches to become a complementary tool to PSG, which is particularly useful for larger-scale preliminary screenings.
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Camera-based sleep monitoring is an emergent research topic in sleep medicine. The feasibility of using both the physiological features and motion features measured by a video camera for sleep staging was not thoroughly investigated. In this paper, we built a camera-based non-contact sleep monitoring setup in the Institute of Respiratory Diseases, Shenzhen People's Hospital, and created a clinical sleep dataset (nocturnal video data of 11 adults) including the expert-corrected PSG references synchronized with the video. The camera-based measurements have shown high correlations with the PSG. It obtains an overall Mean Absolute Error (MAE) of 1.5 bpm for heart-rate (HR), 0.7 bpm for breathing-rate (BR), 13.9 ms for heart-rate variability (HRV), and an accuracy of 93.5% for leg motion detection. The statistical analysis indicates that the averaged HR and variations of BR are distinct features for annotating four sleep stages (awake, REM, light sleep, and deep sleep). HRV parameter (SDNN) can clearly differentiate rapid-eye-movement (REM) and non-REM, while the leg movement is a distinctive feature for separating awake and sleep. The clinical trial demonstrated the feasibility of using physiological and motion features measured by a camera for joint sleep staging, and provides insights for sleep-related feature selection.
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Fases del Sueño , Sueño REM , Adulto , Humanos , Estudios de Factibilidad , Sueño , Fases del Sueño/fisiología , Sueño REM/fisiología , VigiliaRESUMEN
Objective.Sleep apnea has a high incidence and is a potentially dangerous disease, and its early detection and diagnosis are challenging. Polysomnography (PSG) is considered the best approach for sleep apnea detection, but it requires cumbersome and complicated operations. Thus, it cannot satisfy the family healthcare needs.Approach.To facilitate the initial detection of sleep apnea in the home environment, we developed a sleep apnea classification model based on snoring and hybrid neural network, and implemented the well trained model in an embedded hardware platform. We used snore signals from 32 patients at Shenzhen People's Hospital. The Mel-Fbank features were extracted from snore signals to build a sleep apnea classification model based on Bi-LSTM with attention mechanism.Main results.The proposed model classified snore signals into four types: hypopnea, normal condition, obstructive sleep apnea, and central sleep apnea, with 83.52% and 62.31% accuracies, corresponding to the subject-dependence and subject-independence validation, respectively. After pruning and model quantization, at the cost of 0.81% and 0.95% accuracy loss of the subject dependence and subject independence classification, respectively, the number of model parameters and model storage space were reduced by 32.12% and 60.37%, respectively. The model exhibited accuracies of 82.71% and 61.36% based on the subject dependence and subject independence validations, respectively. When the well trained model was successfully porting and running on an STM32 ARM-embedded platform, the model accuracy was 58.85% for the four classifications based on leave-one-subject-out validation.Significance.The proposed sleep apnea detection model can be used in home healthcare for the initial detection of sleep apnea.
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Apnea Obstructiva del Sueño , Ronquido , Humanos , Ronquido/diagnóstico , Proyectos Piloto , Apnea Obstructiva del Sueño/diagnóstico , Polisomnografía/métodosRESUMEN
STUDY OBJECTIVES: Wearable sleep recording devices may be a helpful alternative method for polysomnography (PSG) due to their higher accessibility and comfort as well as lower cost, but their validities need to be examined. The aim of this study was to evaluate the accuracy of a novel single-channel, electroencephalography-based wearable forehead sleep recorder (UMindSleep) to assess sleep staging and oxygen desaturation. METHODS: Two hundred and three Chinese adults recruited from a sleep medicine center underwent an overnight study wearing UMindSleep and PSG simultaneously. Sleep parameters including sleep staging and oxygen desaturation index were compared between UMindSleep and PSG. RESULTS: A total of 195,349 valid epochs from 197 participants (171 with obstructive sleep apnea, 86.8%) were included in analyses of sleep staging. Sensitivities of UMindSleep compared to PSG were 79.7% for wake, 85.8% for light sleep, 79.4% for deep sleep, and 82.7% for rapid eye movement sleep. Specificities were 95.3% for wake, 83.4% for light sleep, 97.0% for deep sleep, and 96.8% for rapid eye movement sleep. Furthermore, the kappa agreements of 0.69-0.79 were indicative of a substantial agreement for sleep staging between UMindSleep and PSG. Sensitivity and specificity regarding oxygen desaturation index were 93.4% and 88.9%, yielding a kappa coefficient of 0.82. CONCLUSIONS: Our findings suggest that UMindSleep may serve as a feasible, accurate, and dependable device for screening of sleep disorders (eg, obstructive sleep apnea) and assessing sleep structure. CITATION: Chen X, Jin X, Zhang J, Ho KW, Wei Y, Cheng H. Validation of a wearable forehead sleep recorder against polysomnography in sleep staging and desaturation events in a clinical sample. J Clin Sleep Med. 2023;19(4):711-718.
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Apnea Obstructiva del Sueño , Dispositivos Electrónicos Vestibles , Adulto , Humanos , Polisomnografía/métodos , Frente , Reproducibilidad de los Resultados , Sueño , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3-6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tag (TMT)-based proteomic analysis was performed in the serum of patients with OSA. The proteomic analysis revealed a set of differentially expressed proteins that may be associated with the pathophysiology of OSA. The differentially expressed proteins in patients with OSA were enriched in pathways including phagosome and glycan synthesis/degradation, immune response, and the hedgehog signaling pathway, indicating that such functions are key targets of OSA. Moreover, the experimental validation studies revealed that four proteins including ANTXR1, COLEC10, NCAM1, and VNN1 were reduced in the serum from patients with moderate and severe OSA, while MAN1A1 and CSPG4 protein levels were elevated in the serum from patients with severe OSA. The protein levels of ANTXR1, COLEC10, NCAM1, and VNN1 were inversely correlated with apnea-hypopnea index (AHI) in the recruited subjects, while the protein level of MAN1A1 was positively correlated with AHI, and no significant correlation was detected between CSPG4 protein and AHI. In summary, the present study for the first time identified differentially expressed proteins in the serum from OSA patients with different severities by using TMT-based proteomic analysis. The functional enrichment studies suggested that several signaling pathways may be associated with the pathophysiology of OSA. The experimental validation results indicated that six proteins including ANTXR1, COLEC10, NCAM1, VNN1, CGPG4, and MAN1A1 may play important roles in the pathophysiology of OSA, which requires further mechanistic investigation.
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Obstructive sleep apnea (OSA) is one of the most common sleep-related breathing disorders and is featured by complete or partial obstruction of the upper airway using sleep. Conflicting reports regarding the association between obstructive sleep apnea (OSA) and cancer incidence are existing in different studies. The aim of this study is to determine whether OSA is independently associated with incidence of all-type cancers by using the meta-analysis. Medline, Embase, PubMed, Ovid, the Cochrane Library database, Web of Science, and Google Scholar were searched by two independent reviewers until 31 January 2021. Studies that evaluated OSA and the cancer incidence were included. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were calculated. Twelve studies, involved 184,915 participants, were pooled in this meta-analysis. Fixed-effects model analysis showed that patients with OSA had an increased risk of cancer incidence (RR: 1.52, 95% CI: 1.39-1.66, P < 0.001). The subgroup analysis showed that the pooled RRs of cancer incidence were 1.14 (95% CI: 1.04-1.25, P = 0.006) for mild OSA, 1.36 (95% CI: 1.32-1.92; P < 0.001) for moderate OSA and 1.59 (95% CI: 1.45-1.74; P < 0.001) for severe OSA, respectively. Patients with moderate and severe OSA were identified to have an increased risk of cancer incidence when compared to patients with mild OSA. In addition, patients with severe OSA also showed an increased risk of incident cancer (RR: 1.18, 95% CI: 1.08-1.28, P < 0.001) when compared to patients with moderate OSA. In conclusion, from most updated literatures, our meta-analysis results indicated that OSA was independently associated with incidence of all-type cancers when stratified the severity of OSA. However, further detailed analysis and clinical studies are warranted to decipher the association between OSA and cancer prevalence.
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Neoplasias , Apnea Obstructiva del Sueño , Humanos , Incidencia , Neoplasias/epidemiología , Oportunidad Relativa , Prevalencia , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiologíaRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) in premature infants is a predominantly secondary occurrence to intrauterine inflammation/infection and postpartum mechanical ventilation; The purpose of this study is to explore the biological roles of lincRNA in the pathogenesis of BPD. METHODS: Newborn rats were randomly assigned to hyperoxia (85% O2) or the control group: the normoxia group (21% O2). Lung tissues were collected on days 1-14. The BPD animal model was validated using HE staining, Masson staining, and real-time RT-PCR. Deep Illumina sequencing was used to reveal the differential expression of long non-coding RNAs in hyperoxia bronchopulmonary dysplasia rat models. KEGG and GO functions were predicted. Nine possible BPD-related target lincRNAs were verified by RTq-PCR. RESULTS: The histopathologic changes in lung tissues manifested as hyperaemia, edema, hemorrhage, and inflammation cell infiltration after continuous exposure to hyperoxia for 3 days, and became aggravated after 7 days of hyperoxic exposure. The above lung tissue inflammatory manifestations were alleviated and taken over by pulmonary interstitia hyperplasia and fibrocyte proliferation after 14 days of hyperoxic exposure. The expressions of lincRNA differed between the hyperoxia bronchopulmonary dysplasia model group and the normoxia group. 1175 different lincRNAs were detected in the hyperoxia group and the normoxia group, of which 544 were up-regulated and 631 were down-regulated. 673 moleculars related to GO functions were enriched, including cell location and biological process. Pathway enrichment analysis showed that lincRNA was involved in 257 KEGG pathways. 9 lincRNA were validated in the sample, and the difference was statistically significant. CONCLUSION: LincRNAs were identified differently between the BPD model and the normoxia group. Many target genes were involved in the developmental process, including cell component biogenesis, biological regulation, transcription regulator, and translation regulator. The BPD might be caused by the activation of the pathways of the EMC-receptor interaction, cytokine-cytokine receptor interaction, cell cycle, and cell adhesion molecules. The present study provides new insight into the pathogenesis mechanism of BPD.
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The aim of this study was to investigate the in vitro effect of interleukin-24 (IL-24) on apoptosis of bone marrow mononuclear cells (BMMNC) in children with acute leukemia. Every group of acute lymphocytic leukemia (ALL) and acute myeloid leukemia (ANLL) had 20 children who did not receive any therapy. The bone marrow was taken from patients and controls, the MNC were isolated from bone marrow, DNA was detected by glucose electrophoresis. Apoptosis of BMMNC was assayed by flow cytometry with propidium iodine staining. RT-PCR was used to detect the expression level of bcl-2, caspase-3 mRNA, and to analyze the effect of IL-24 on them. The results showed that the IL-24 induced apoptosis of BMMNC in children with acute leukemia. After acute leukemia BMMNC were exposed to IL-24 for 48 hours, DNA ladder fragment appeared, and the apoptotic rate of the group treated with IL-24 of 50 ng/ml was obviously higher than that of the control group (0 ng/ml). IL-24 decreased the bcl-2 mRNA expression level, enhanced caspase-3 mRNA expression level of BMMNC from AL patients. It is concluded that the IL-24 can induce apoptosis of AL BMMNC in vitro, which may be due to decreasing of bcl-2 mRNA level and enhancing of caspase-3 mRNA level.