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Causal Associations Between Sleep Traits and Delirium: A Bidirectional Two-Sample Mendelian Randomization Study.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-21 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S491216
Hao Liu, Zhengze Zhang, Yuewen He, Longfei Ding, Tong Wu, Yong Wang, Wuhua Ma

Purpose: Numerous studies have identified a correlation between sleep and delirium; however, the causal relationship remains ambiguous. This bidirectional two-sample Mendelian randomization (MR) study was conducted to examine the possible causal relationships between sleep traits and delirium.

Patients and methods: Utilizing genome-wide association studies (GWAS), we identified ten sleep traits: chronotype, sleep duration, short sleep duration, long sleep duration, daytime napping, daytime sleepiness, insomnia, number of sleep episodes (NSE), sleep efficiency, and rapid eye movement sleep behavior disorder (RBD). In this MR study, genetic variants independently associated with exposures were selected as instrumental variables (IVs). To establish causal inferences, three regression models were employed-inverse variance weighted (IVW), MR Egger, and weighted median (WM) -and conducted sensitivity analyses to assess the robustness of our findings.

Results: Our results suggest no significant causal association between the ten sleep traits and the risk of delirium. The reverse MR analysis revealed that delirium is associated with an increased propensity for morning chronotype [ORIVW, 1.025; 95% CI, 1.012-1.036; p = 1.50E-05; adjusted p values (padjusted)= 1.35E-04] and a decreased risk of long sleep duration [ORIVW, 0.996; 95% CI, 0.993-0.999; p = 0.013; padjusted= 0.059]. However, no robust evidence currently exists to substantiate a causal relationship between delirium and other sleep traits.

Conclusion: Our bidirectional, two-sample MR analysis study did not provide definitive evidence that sleep traits may augment the susceptibility to delirium. However, the reverse MR results indicate that delirium may predispose patients to an earlier sleep-wake cycle. Additional large-scale investigations are necessary to examine the bidirectional causality between delirium and sleep traits.

{"title":"Causal Associations Between Sleep Traits and Delirium: A Bidirectional Two-Sample Mendelian Randomization Study.","authors":"Hao Liu, Zhengze Zhang, Yuewen He, Longfei Ding, Tong Wu, Yong Wang, Wuhua Ma","doi":"10.2147/NSS.S491216","DOIUrl":"10.2147/NSS.S491216","url":null,"abstract":"<p><strong>Purpose: </strong>Numerous studies have identified a correlation between sleep and delirium; however, the causal relationship remains ambiguous. This bidirectional two-sample Mendelian randomization (MR) study was conducted to examine the possible causal relationships between sleep traits and delirium.</p><p><strong>Patients and methods: </strong>Utilizing genome-wide association studies (GWAS), we identified ten sleep traits: chronotype, sleep duration, short sleep duration, long sleep duration, daytime napping, daytime sleepiness, insomnia, number of sleep episodes (NSE), sleep efficiency, and rapid eye movement sleep behavior disorder (RBD). In this MR study, genetic variants independently associated with exposures were selected as instrumental variables (IVs). To establish causal inferences, three regression models were employed-inverse variance weighted (IVW), MR Egger, and weighted median (WM) -and conducted sensitivity analyses to assess the robustness of our findings.</p><p><strong>Results: </strong>Our results suggest no significant causal association between the ten sleep traits and the risk of delirium. The reverse MR analysis revealed that delirium is associated with an increased propensity for morning chronotype [OR<sub>IVW</sub>, 1.025; 95% CI, 1.012-1.036; p = 1.50E-05; adjusted p values (p<sub>adjusted</sub>)= 1.35E-04] and a decreased risk of long sleep duration [OR<sub>IVW</sub>, 0.996; 95% CI, 0.993-0.999; p = 0.013; p<sub>adjusted</sub>= 0.059]. However, no robust evidence currently exists to substantiate a causal relationship between delirium and other sleep traits.</p><p><strong>Conclusion: </strong>Our bidirectional, two-sample MR analysis study did not provide definitive evidence that sleep traits may augment the susceptibility to delirium. However, the reverse MR results indicate that delirium may predispose patients to an earlier sleep-wake cycle. Additional large-scale investigations are necessary to examine the bidirectional causality between delirium and sleep traits.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2171-2181"},"PeriodicalIF":3.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Craniofacial Development Characteristics in Children with Obstructive Sleep Apnea for Establishment and External Validation of the Prediction Model.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-21 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S492714
Yonglong Su, Zitong Wang, Huanhuan Chang, Simin Zhu, Yanuo Zhou, Zine Cao, Lina Ma, Yuqi Yuan, Yushan Xie, Xiaoxin Niu, Chendi Lu, Yitong Zhang, Haiqin Liu, Na Shao, Libo Yin, Chao Si, Xiaoyong Ren, Yewen Shi

Purpose: Aimed to analyze the developmental characteristics of craniofacial structures and soft tissues in children with obstructive sleep apnea (OSA) and to establish and evaluate prediction model.

Methods: It's a retrospective study comprising 747 children aged 2-12 years (337 patients and 410 controls) visited the Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University (July 2017 to March 2024). Lateral head radiographs were obtained to compare the cephalometric measurements. The clinical prediction model was constructed using LASSO regression analysis. We analyzed 300 children from the Xi'an Children's Hospital for external validation.

Results: Children with OSA had a higher body mass, a higher tonsil grade, larger AN ratio (ratio of the adenoids to the skeletal upper airway width), larger radius of the tonsils, a smaller angle between the skull base and maxilla (SNA) and smaller angle between the skull base and mandible (SNB), a larger distance from the hyoid to the mandibular plane (H-MP) and smaller distance between the third cervical vertebra and hyoid (H-C), a larger thickness of the soft palate (SPT) and smaller inclination angle of the soft palate than those of the controls (all p < 0.05). A prediction model was constructed for 2-12 years group (AUC of 0.812 [95% CI: 0.781-0.842]). Age-specific prediction models were developed for preschool children (AUC of 0.769 [95% CI: 0.725-0.814]), for school-aged children (AUC of 0.854 [95% CI: 0.812-0.895]).

Conclusion: Our study findings support the important role of craniofacial structures such as the hyoid, maxilla, mandible, and soft palate in pediatric OSA. Age-stratified predictive models for pediatric OSA indicated varying parameters across different age groups which underscore the necessity for stratifying by age in future research. The prediction model designed will greatly assist health care practitioners with rapidly identifying.

{"title":"Craniofacial Development Characteristics in Children with Obstructive Sleep Apnea for Establishment and External Validation of the Prediction Model.","authors":"Yonglong Su, Zitong Wang, Huanhuan Chang, Simin Zhu, Yanuo Zhou, Zine Cao, Lina Ma, Yuqi Yuan, Yushan Xie, Xiaoxin Niu, Chendi Lu, Yitong Zhang, Haiqin Liu, Na Shao, Libo Yin, Chao Si, Xiaoyong Ren, Yewen Shi","doi":"10.2147/NSS.S492714","DOIUrl":"10.2147/NSS.S492714","url":null,"abstract":"<p><strong>Purpose: </strong>Aimed to analyze the developmental characteristics of craniofacial structures and soft tissues in children with obstructive sleep apnea (OSA) and to establish and evaluate prediction model.</p><p><strong>Methods: </strong>It's a retrospective study comprising 747 children aged 2-12 years (337 patients and 410 controls) visited the Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University (July 2017 to March 2024). Lateral head radiographs were obtained to compare the cephalometric measurements. The clinical prediction model was constructed using LASSO regression analysis. We analyzed 300 children from the Xi'an Children's Hospital for external validation.</p><p><strong>Results: </strong>Children with OSA had a higher body mass, a higher tonsil grade, larger AN ratio (ratio of the adenoids to the skeletal upper airway width), larger radius of the tonsils, a smaller angle between the skull base and maxilla (SNA) and smaller angle between the skull base and mandible (SNB), a larger distance from the hyoid to the mandibular plane (H-MP) and smaller distance between the third cervical vertebra and hyoid (H-C), a larger thickness of the soft palate (SPT) and smaller inclination angle of the soft palate than those of the controls (all <i>p</i> < 0.05). A prediction model was constructed for 2-12 years group (AUC of 0.812 [95% CI: 0.781-0.842]). Age-specific prediction models were developed for preschool children (AUC of 0.769 [95% CI: 0.725-0.814]), for school-aged children (AUC of 0.854 [95% CI: 0.812-0.895]).</p><p><strong>Conclusion: </strong>Our study findings support the important role of craniofacial structures such as the hyoid, maxilla, mandible, and soft palate in pediatric OSA. Age-stratified predictive models for pediatric OSA indicated varying parameters across different age groups which underscore the necessity for stratifying by age in future research. The prediction model designed will greatly assist health care practitioners with rapidly identifying.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2151-2170"},"PeriodicalIF":3.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Sleep Fragmentation and Arousal on Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea: A Cross-Sectional Study.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-20 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S480186
Yue Zhong, Biying Wang, Jiefeng Huang, Meixin Nian, Jianming Zhao, Gongping Chen

Purpose: Obstructive sleep apnea (OSA) is a contributing factor to nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the clinical and polysomnographic characteristics of OSA patients with and without NAFLD, focusing on the relationships between sleep fragmentation, arousal and NAFLD.

Materials and methods: We consecutively enrolled patients who underwent polysomnography, anthropometry, blood sampling, and abdominal ultrasonography. Patients were categorized into NAFLD and non-NAFLD groups. A comparative analysis of clinical and polysomnographic profiles was conducted, followed by multivariate binary logistic regression to explore the relationship between sleep disturbance indices and NAFLD.

Results: A total of 403 subjects were included, including 92 patients with NAFLD and 311 with non-NAFLD. NAFLD patients exhibited a greater apnea-hypopnea index (AHI) (51.19/h vs 33.60/h, p = 0.002) and oxygen desaturation index (ODI) (37.90/h vs 21.40/h, p=0.034) compared to non-NAFLD patients. Specifically, NAFLD patients had a higher rapid eye movement (REM)-AHI (53.70/h vs 43.60/h, p=0.001) and greater arousal index (AI) (32 vs 25, p = 0.009). Additionally, sleep latency (SL) was significantly lower in the NAFLD group (p < 0.05). Multivariate logistic regression analysis confirmed that REM-AHI (OR=1.023, p = 0.024), AI (OR=1.140, p = 0.01), and SL (OR=0.956, p = 0.035) were significantly associated with NAFLD in OSA patients.

Conclusion: This study revealed that sleep disturbance indices, especially AI, REM-AHI and SL, were closely related to NAFLD. When evaluating whether OSA patients are complicated with NAFLD, more attention should be given to sleep fragmentation and arousal.

{"title":"Impact of Sleep Fragmentation and Arousal on Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea: A Cross-Sectional Study.","authors":"Yue Zhong, Biying Wang, Jiefeng Huang, Meixin Nian, Jianming Zhao, Gongping Chen","doi":"10.2147/NSS.S480186","DOIUrl":"10.2147/NSS.S480186","url":null,"abstract":"<p><strong>Purpose: </strong>Obstructive sleep apnea (OSA) is a contributing factor to nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the clinical and polysomnographic characteristics of OSA patients with and without NAFLD, focusing on the relationships between sleep fragmentation, arousal and NAFLD.</p><p><strong>Materials and methods: </strong>We consecutively enrolled patients who underwent polysomnography, anthropometry, blood sampling, and abdominal ultrasonography. Patients were categorized into NAFLD and non-NAFLD groups. A comparative analysis of clinical and polysomnographic profiles was conducted, followed by multivariate binary logistic regression to explore the relationship between sleep disturbance indices and NAFLD.</p><p><strong>Results: </strong>A total of 403 subjects were included, including 92 patients with NAFLD and 311 with non-NAFLD. NAFLD patients exhibited a greater apnea-hypopnea index (AHI) (51.19/h vs 33.60/h, p = 0.002) and oxygen desaturation index (ODI) (37.90/h vs 21.40/h, p=0.034) compared to non-NAFLD patients. Specifically, NAFLD patients had a higher rapid eye movement (REM)-AHI (53.70/h vs 43.60/h, p=0.001) and greater arousal index (AI) (32 vs 25, p = 0.009). Additionally, sleep latency (SL) was significantly lower in the NAFLD group (p < 0.05). Multivariate logistic regression analysis confirmed that REM-AHI (OR=1.023, p = 0.024), AI (OR=1.140, p = 0.01), and SL (OR=0.956, p = 0.035) were significantly associated with NAFLD in OSA patients.</p><p><strong>Conclusion: </strong>This study revealed that sleep disturbance indices, especially AI, REM-AHI and SL, were closely related to NAFLD. When evaluating whether OSA patients are complicated with NAFLD, more attention should be given to sleep fragmentation and arousal.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2143-2150"},"PeriodicalIF":3.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TRPC5 Promotes Intermittent Hypoxia-Induced Cardiomyocyte Injury Through Oxidative Stress.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S494748
Xuan Qiu, Yanli Yao, Yulan Chen, Yu Li, Xiaojing Sun, Xiaoli Zhu

Purpose: Intermittent hypoxia (IH), a defining feature of obstructive sleep apnea (OSA), is associated with heart damage and linked to transient receptor potential canonical channel 5 (TRPC5). Nonetheless, the function of TRPC5 in OSA-induced cardiac injury remains uncertain. For this research, we aimed to explore the role and potential mechanism of TRPC5 in cardiomyocyte injury induced by intermittent hypoxia.

Methods: 30 patients with newly diagnosed OSA and 30 patients with primary snoring(PS) were included in this study. Participants were subjected to polysomnography (PSG) for OSA diagnosis. Echocardiography was used to evaluate the structure and function of the heart, while peripheral blood samples were obtained. Additionally, RT-qPCR was utilized to quantify the relative expression level of TRPC5 mRNA in peripheral blood. H9c2 cells experienced IH or normoxia. TRPC5 levels in H9c2 cells were determined via RT-qPCR and Western blotting (WB) methods. H9c2 cells overexpressing TRPC5 were subjected to either normoxic or intermittent hypoxia conditions. Cell viability was determined by CCK8, the apoptosis rate, reactive oxygen species(ROS) levels, and Ca2+ concentration were assessed by flow cytometry, and the protein levels of TRPC5, Bcl-2, Bax, and Caspase-3 were analyzed by WB. Mitochondrial membrane potential(MMP), mitochondrial membrane permeability transition pore(mPTP), and transmission electron microscopy(TEM) were employed to observe mitochondrial function and structure. After inhibiting ROS with N-acetylcysteine (NAC), apoptosis, mitochondrial function and structure, and the concentration of Ca2+ were further detected.

Results: TRPC5 and left atrial diameter (LAD) were higher in OSA individuals, while the E/A ratio was lower(all P<0.05). IH impaired cell viability, triggered cell apoptosis, and enhanced TRPC5 expression in H9c2 cells(all P<0.05). The effects of IH on apoptosis, cell viability, mitochondrial function and structure damage, and oxidative stress (OxS) in H9c2 cells were accelerated by the overexpression of TRPC5(all P<0.05). Furthermore, cell apoptosis and mitochondrial structural and functional damage caused by overexpression of TRPC5 were attenuated by ROS inhibition.

Conclusion: TRPC5 is associated with structural and functional cardiac damage in patients with OSA, and TRPC5 promotes IH-induced apoptosis and mitochondrial damage in cardiomyocytes through OxS. TRPC5 may be a novel target for the diagnosis and treatment of OSA-induced myocardial injury.

{"title":"TRPC5 Promotes Intermittent Hypoxia-Induced Cardiomyocyte Injury Through Oxidative Stress.","authors":"Xuan Qiu, Yanli Yao, Yulan Chen, Yu Li, Xiaojing Sun, Xiaoli Zhu","doi":"10.2147/NSS.S494748","DOIUrl":"10.2147/NSS.S494748","url":null,"abstract":"<p><strong>Purpose: </strong>Intermittent hypoxia (IH), a defining feature of obstructive sleep apnea (OSA), is associated with heart damage and linked to transient receptor potential canonical channel 5 (TRPC5). Nonetheless, the function of TRPC5 in OSA-induced cardiac injury remains uncertain. For this research, we aimed to explore the role and potential mechanism of TRPC5 in cardiomyocyte injury induced by intermittent hypoxia.</p><p><strong>Methods: </strong>30 patients with newly diagnosed OSA and 30 patients with primary snoring(PS) were included in this study. Participants were subjected to polysomnography (PSG) for OSA diagnosis. Echocardiography was used to evaluate the structure and function of the heart, while peripheral blood samples were obtained. Additionally, RT-qPCR was utilized to quantify the relative expression level of TRPC5 mRNA in peripheral blood. H9c2 cells experienced IH or normoxia. TRPC5 levels in H9c2 cells were determined via RT-qPCR and Western blotting (WB) methods. H9c2 cells overexpressing TRPC5 were subjected to either normoxic or intermittent hypoxia conditions. Cell viability was determined by CCK8, the apoptosis rate, reactive oxygen species(ROS) levels, and Ca<sup>2+</sup> concentration were assessed by flow cytometry, and the protein levels of TRPC5, Bcl-2, Bax, and Caspase-3 were analyzed by WB. Mitochondrial membrane potential(MMP), mitochondrial membrane permeability transition pore(mPTP), and transmission electron microscopy(TEM) were employed to observe mitochondrial function and structure. After inhibiting ROS with N-acetylcysteine (NAC), apoptosis, mitochondrial function and structure, and the concentration of Ca<sup>2+</sup> were further detected.</p><p><strong>Results: </strong>TRPC5 and left atrial diameter (LAD) were higher in OSA individuals, while the E/A ratio was lower(all <i>P</i><0.05). IH impaired cell viability, triggered cell apoptosis, and enhanced TRPC5 expression in H9c2 cells(all <i>P</i><0.05). The effects of IH on apoptosis, cell viability, mitochondrial function and structure damage, and oxidative stress (OxS) in H9c2 cells were accelerated by the overexpression of TRPC5(all <i>P</i><0.05). Furthermore, cell apoptosis and mitochondrial structural and functional damage caused by overexpression of TRPC5 were attenuated by ROS inhibition.</p><p><strong>Conclusion: </strong>TRPC5 is associated with structural and functional cardiac damage in patients with OSA, and TRPC5 promotes IH-induced apoptosis and mitochondrial damage in cardiomyocytes through OxS. TRPC5 may be a novel target for the diagnosis and treatment of OSA-induced myocardial injury.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2125-2141"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self-Reported Symptoms of Obstructive Sleep Apnea are Associated with Increased Risk of Kidney Stones: A Cross-Sectional Study from NHANES 2015-2020.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-18 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S491657
Dongru Du, Jianjun Luo, Weiling Cai, Jiangyue Qin, Yao Yang, Xueru Hu, Xiaohua Li, Fengming Luo, Yongchun Shen

Objective: To investigate whether self-reported symptoms of obstructive sleep apnea (OSA), including snoring, snorting/stopping breathing, and sleepiness, are associated with increased risk of kidney stones.

Methods: This cross-sectional study was conducted based on the 2015-2020 National Health and Nutrition Examination Survey (NHANES). Self-reported symptoms of OSA and history of kidney stones were diagnosed via questionnaires. Multivariable logistic regression was used to determine the associations between self-reported symptoms of OSA and kidney stones. Subgroup analyses and interaction tests were performed to address this issue further.

Results: A total of 9,973 participants were enrolled, and the prevalence of kidney stones was 10.76%. Although no significant association was observed between frequent snoring and kidney stones after covariate adjustments (OR 1.033, 95% CI 0.726, 1.469 p = 0.850), frequent snorting/stopping breathing was associated with a greater risk of kidney stones after covariate adjustments (OR 1.655, 95% CI 1.262, 2.172, p = 0.002). Participants who often or almost always felt sleepy also had a greater risk of kidney stones after covariate adjustment (OR 1.651, 95% CI 1.222, 2.229; p = 0.004). The interaction tests suggested that marital status (p = 0.015) and smoking status (p < 0.001) significantly interacted with the association between snorting/stopping breathing and kidney stones.

Conclusion: Self-reported frequent snorting/stopping breathing and sleepiness may be associated with increased risk of kidney stones. Although these findings may emphasize prevention of kidney stones in these people, further research was still needed to verify our results.

{"title":"Self-Reported Symptoms of Obstructive Sleep Apnea are Associated with Increased Risk of Kidney Stones: A Cross-Sectional Study from NHANES 2015-2020.","authors":"Dongru Du, Jianjun Luo, Weiling Cai, Jiangyue Qin, Yao Yang, Xueru Hu, Xiaohua Li, Fengming Luo, Yongchun Shen","doi":"10.2147/NSS.S491657","DOIUrl":"10.2147/NSS.S491657","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether self-reported symptoms of obstructive sleep apnea (OSA), including snoring, snorting/stopping breathing, and sleepiness, are associated with increased risk of kidney stones.</p><p><strong>Methods: </strong>This cross-sectional study was conducted based on the 2015-2020 National Health and Nutrition Examination Survey (NHANES). Self-reported symptoms of OSA and history of kidney stones were diagnosed via questionnaires. Multivariable logistic regression was used to determine the associations between self-reported symptoms of OSA and kidney stones. Subgroup analyses and interaction tests were performed to address this issue further.</p><p><strong>Results: </strong>A total of 9,973 participants were enrolled, and the prevalence of kidney stones was 10.76%. Although no significant association was observed between frequent snoring and kidney stones after covariate adjustments (OR 1.033, 95% CI 0.726, 1.469 p = 0.850), frequent snorting/stopping breathing was associated with a greater risk of kidney stones after covariate adjustments (OR 1.655, 95% CI 1.262, 2.172, p = 0.002). Participants who often or almost always felt sleepy also had a greater risk of kidney stones after covariate adjustment (OR 1.651, 95% CI 1.222, 2.229; p = 0.004). The interaction tests suggested that marital status (p = 0.015) and smoking status (p < 0.001) significantly interacted with the association between snorting/stopping breathing and kidney stones.</p><p><strong>Conclusion: </strong>Self-reported frequent snorting/stopping breathing and sleepiness may be associated with increased risk of kidney stones. Although these findings may emphasize prevention of kidney stones in these people, further research was still needed to verify our results.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2099-2110"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Continuous Positive Airway Pressure Treatment on Sawtooth Waves During Rapid Eye Movement Sleep in Obstructive Sleep Apnea Patients.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S489288
Yuhao Mao, Qi Li, Xueliang Zou, Zhijun Zhong, Qian Ouyang, Chunmei Gan, Fang Yi, Yaxing Luo, Zilin Cheng, Dongyuan Yao

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder characterized by recurrent upper airway collapse and obstruction, leading to reduced or absent breathing during sleep, especially rapid eye movement (REM) sleep, and continuous positive airway pressure treatment (CPAP) is often used for treatment of OSA. Sawtooth waves (STWs) are a characteristic of REM sleep.

Objective: To examine effects of CPAP treatment on STWs during REM sleep in the OSA patients.

Methods: Polysomnographic recordings were performed on 20 moderate-to-severe OSA patients and 16 normal controls, and comparisons of STWs during REM sleep in the OSA patients with and without CPAP treatment (paired t-test or Wilcoxon signed-rank test wherever appropriate), and between OSA patients and normal controls (Student's t-test or Wilcoxon rank-sum test) were carried out. In addition, linear correlation analyses were used to estimate the relationship of STWs and REM sleep with duration of non-REM (NREM) sleep stage 3 (N3).

Results: The STWs were classified to be apnea/hypopnea associated and not associated (isolated), and the amplitude of the isolated STWs was significantly higher than that of the apnea/hypopnea associated. With CPAP treatment, the percentage of REM sleep with STWs and the amplitude of STWs were significantly increased to the levels, which were not significantly different from those in the normal controls, while the frequency of STWs was not significantly changed. In addition, the total duration of REM sleep and the duration of REM sleep with STWs were both positively correlated with the duration of N3 sleep in the normal controls and the OSA patients with CPAP treatment. Furthermore, CPAP treatment also caused a significant increase in the duration of rapid eye movements in REM sleep.

Conclusion: These findings suggest that there are some interconnections between NREM and REM sleep, and STWs not only represent the quality of REM sleep but also are correlated with N3 sleep.

{"title":"Effects of Continuous Positive Airway Pressure Treatment on Sawtooth Waves During Rapid Eye Movement Sleep in Obstructive Sleep Apnea Patients.","authors":"Yuhao Mao, Qi Li, Xueliang Zou, Zhijun Zhong, Qian Ouyang, Chunmei Gan, Fang Yi, Yaxing Luo, Zilin Cheng, Dongyuan Yao","doi":"10.2147/NSS.S489288","DOIUrl":"10.2147/NSS.S489288","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder characterized by recurrent upper airway collapse and obstruction, leading to reduced or absent breathing during sleep, especially rapid eye movement (REM) sleep, and continuous positive airway pressure treatment (CPAP) is often used for treatment of OSA. Sawtooth waves (STWs) are a characteristic of REM sleep.</p><p><strong>Objective: </strong>To examine effects of CPAP treatment on STWs during REM sleep in the OSA patients.</p><p><strong>Methods: </strong>Polysomnographic recordings were performed on 20 moderate-to-severe OSA patients and 16 normal controls, and comparisons of STWs during REM sleep in the OSA patients with and without CPAP treatment (paired <i>t</i>-test or Wilcoxon signed-rank test wherever appropriate), and between OSA patients and normal controls (Student's <i>t</i>-test or Wilcoxon rank-sum test) were carried out. In addition, linear correlation analyses were used to estimate the relationship of STWs and REM sleep with duration of non-REM (NREM) sleep stage 3 (N3).</p><p><strong>Results: </strong>The STWs were classified to be apnea/hypopnea associated and not associated (isolated), and the amplitude of the isolated STWs was significantly higher than that of the apnea/hypopnea associated. With CPAP treatment, the percentage of REM sleep with STWs and the amplitude of STWs were significantly increased to the levels, which were not significantly different from those in the normal controls, while the frequency of STWs was not significantly changed. In addition, the total duration of REM sleep and the duration of REM sleep with STWs were both positively correlated with the duration of N3 sleep in the normal controls and the OSA patients with CPAP treatment. Furthermore, CPAP treatment also caused a significant increase in the duration of rapid eye movements in REM sleep.</p><p><strong>Conclusion: </strong>These findings suggest that there are some interconnections between NREM and REM sleep, and STWs not only represent the quality of REM sleep but also are correlated with N3 sleep.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2111-2124"},"PeriodicalIF":3.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
White Matter Imaging Phenotypes Mediate the Negative Causality of Mitochondrial DNA Copy Number on Sleep Apnea: A Bidirectional Mendelian Randomization Study and Mediation Analysis. 白质成像表型介导线粒体 DNA 拷贝数对睡眠呼吸暂停的负因果关系:双向孟德尔随机化研究与中介分析
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S487782
Qiaohui Ying, Mingwei Wang, Zichen Zhao, Yongwei Wu, Changyun Sun, Xinyi Huang, Xin Zhang, Jie Guo

Purpose: Sleep apnea (SA), associated with absent neural output, is characterised by recurrent episodes of hypoxemia and repeated arousals during sleep, resulting in decreased sleep quality and various health complications. Mitochondrial DNA copy number (mtDNA-CN), an easily accessible biomarker in blood, reflects mitochondrial function. However, the causal relationship between mtDNA-CN and SA remains unclear. This study aimed to investigate the causality between mtDNA-CN and SA while identifying potential mediating brain imaging phenotypes (BIPs).

Methods: Two-sample bidirectional Mendelian randomisation (MR) analysis was performed to estimate the causal relationship between mtDNA-CN and SA, with further validation using Bayesian framework-based MR analysis. A two-step approach was employed to evaluate causal relationships between BIPs, mtDNA-CN and SA, utilising the "product of coefficients" method to assess the mediating effects of BIPs. Multiple testing errors were corrected using the Benjamini-Hochberg method.

Results: Genetically predicted mtDNA-CN had a negative causal effect on SA (OR = 0.859, 95% CI = 0.785-0.939, P = 3.20×10-4), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954-1.0159, P = 0.2825). Among 3935 BIPs, two features related to white matter microstructure served as partial mediators: the second eigenvalue from diffusion MRI data analysed by tract-based spatial statistics in the right posterior thalamic radiation, with a mediation proportion of 11.37% (P = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% (P = 0.0323).

Conclusion: This study demonstrated a causal relationship between mtDNA-CN and SA, with specific brain white matter microstructure phenotypes potentially acting as mediators. These findings highlight the potential of mtDNA-CN as a biomarker for SA and underscore its relevance in guiding future therapeutic strategies targeting mitochondrial health and brain white matter microstructure.

{"title":"White Matter Imaging Phenotypes Mediate the Negative Causality of Mitochondrial DNA Copy Number on Sleep Apnea: A Bidirectional Mendelian Randomization Study and Mediation Analysis.","authors":"Qiaohui Ying, Mingwei Wang, Zichen Zhao, Yongwei Wu, Changyun Sun, Xinyi Huang, Xin Zhang, Jie Guo","doi":"10.2147/NSS.S487782","DOIUrl":"10.2147/NSS.S487782","url":null,"abstract":"<p><strong>Purpose: </strong>Sleep apnea (SA), associated with absent neural output, is characterised by recurrent episodes of hypoxemia and repeated arousals during sleep, resulting in decreased sleep quality and various health complications. Mitochondrial DNA copy number (mtDNA-CN), an easily accessible biomarker in blood, reflects mitochondrial function. However, the causal relationship between mtDNA-CN and SA remains unclear. This study aimed to investigate the causality between mtDNA-CN and SA while identifying potential mediating brain imaging phenotypes (BIPs).</p><p><strong>Methods: </strong>Two-sample bidirectional Mendelian randomisation (MR) analysis was performed to estimate the causal relationship between mtDNA-CN and SA, with further validation using Bayesian framework-based MR analysis. A two-step approach was employed to evaluate causal relationships between BIPs, mtDNA-CN and SA, utilising the \"product of coefficients\" method to assess the mediating effects of BIPs. Multiple testing errors were corrected using the Benjamini-Hochberg method.</p><p><strong>Results: </strong>Genetically predicted mtDNA-CN had a negative causal effect on SA (OR = 0.859, 95% CI = 0.785-0.939, <i>P</i> = 3.20×10<sup>-4</sup>), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954-1.0159, <i>P</i> = 0.2825). Among 3935 BIPs, two features related to white matter microstructure served as partial mediators: the second eigenvalue from diffusion MRI data analysed by tract-based spatial statistics in the right posterior thalamic radiation, with a mediation proportion of 11.37% (<i>P</i> = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% (<i>P</i> = 0.0323).</p><p><strong>Conclusion: </strong>This study demonstrated a causal relationship between mtDNA-CN and SA, with specific brain white matter microstructure phenotypes potentially acting as mediators. These findings highlight the potential of mtDNA-CN as a biomarker for SA and underscore its relevance in guiding future therapeutic strategies targeting mitochondrial health and brain white matter microstructure.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2045-2061"},"PeriodicalIF":3.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosomes from IH- Induced bEnd3 Cells Promote OSA Cognitive Impairment via miR-20a-5p/MFN2 Mediated Pyroptosis of HT22 Cells.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S485952
Zhifeng Chen, Yulin Shang, Yanru Ou, Li Zhou, Ting Liu, Subo Gong, Xudong Xiang, Yating Peng, Ruoyun Ouyang

Background: OSA can cause cognitive impairment (CI). The aim of this study was to investigate whether miR-20a-5p in exosomes derived from bEnd3 cells with IH mediates intercellular crosstalk and induces CI through hippocampal neuronal cell pyroptosis.

Materials and methods: BEnd3-derived exosomes were isolated from the normal oxygen control group (NC-EXOS) and IH group (IH-EXOS). In vitro, exosomes were cocultured with HT22 cells. Meanwhile, in vivo, exosomes were injected into mice via the caudal vein. The spatial memory ability of mice was tested by MWM method to evaluate the effect of exosomes on the cognitive function of mice. Adults diagnosed with OSA underwent the MoCA and ESS tests to assess cognitive function and daytime sleepiness. Spearman's rank correlation analysis was used to evaluate the correlation between miR-20a-5p and candidate proteins and clinical parameters. Transfection using small interfering RNAs, miRNA mimics, and plasmids to evaluate the role of miR-20a-5p and its target genes. Dual luciferase reporter gene assay was used to confirm the binding of miR-20a-5p to its target gene.

Results: IH could cause pyroptosis and inflammation in bEnd3 cells, and promote the expression of miR-20a-5p. Isolated IH-EXOS induced increased pyroptosis and activation of inflammatory response in vitro and in vivo, accompanied by increased expression of miR-20a-5p. In addition, IH-EXOS led to decreased learning and memory ability in mice. Interestingly, AHI was higher and MoCA scores were lower in severe OSA compared to healthy comparisons. In addition, miR-20a-5p and GSDMD were positively correlated with AHI but negatively correlated with MoCA in severe OSA. IH-induced exosomes were rich in miR-20a-5p, and these exosomes were found to deliver miR-20a-5p to HT22 cells, playing a key role in the induction of OSA-CI by directly targeting MFN2.

Conclusion: Exosome miR-20a-5p from IH-stimulated bEnd3 cells can promote OSA-CI by increasing HT22 cells pyroptosis through its target MFN2.

{"title":"Exosomes from IH- Induced bEnd3 Cells Promote OSA Cognitive Impairment via miR-20a-5p/MFN2 Mediated Pyroptosis of HT22 Cells.","authors":"Zhifeng Chen, Yulin Shang, Yanru Ou, Li Zhou, Ting Liu, Subo Gong, Xudong Xiang, Yating Peng, Ruoyun Ouyang","doi":"10.2147/NSS.S485952","DOIUrl":"10.2147/NSS.S485952","url":null,"abstract":"<p><strong>Background: </strong>OSA can cause cognitive impairment (CI). The aim of this study was to investigate whether miR-20a-5p in exosomes derived from bEnd3 cells with IH mediates intercellular crosstalk and induces CI through hippocampal neuronal cell pyroptosis.</p><p><strong>Materials and methods: </strong>BEnd3-derived exosomes were isolated from the normal oxygen control group (NC-EXOS) and IH group (IH-EXOS). In vitro, exosomes were cocultured with HT22 cells. Meanwhile, in vivo, exosomes were injected into mice via the caudal vein. The spatial memory ability of mice was tested by MWM method to evaluate the effect of exosomes on the cognitive function of mice. Adults diagnosed with OSA underwent the MoCA and ESS tests to assess cognitive function and daytime sleepiness. Spearman's rank correlation analysis was used to evaluate the correlation between miR-20a-5p and candidate proteins and clinical parameters. Transfection using small interfering RNAs, miRNA mimics, and plasmids to evaluate the role of miR-20a-5p and its target genes. Dual luciferase reporter gene assay was used to confirm the binding of miR-20a-5p to its target gene.</p><p><strong>Results: </strong>IH could cause pyroptosis and inflammation in bEnd3 cells, and promote the expression of miR-20a-5p. Isolated IH-EXOS induced increased pyroptosis and activation of inflammatory response in vitro and in vivo, accompanied by increased expression of miR-20a-5p. In addition, IH-EXOS led to decreased learning and memory ability in mice. Interestingly, AHI was higher and MoCA scores were lower in severe OSA compared to healthy comparisons. In addition, miR-20a-5p and GSDMD were positively correlated with AHI but negatively correlated with MoCA in severe OSA. IH-induced exosomes were rich in miR-20a-5p, and these exosomes were found to deliver miR-20a-5p to HT22 cells, playing a key role in the induction of OSA-CI by directly targeting MFN2.</p><p><strong>Conclusion: </strong>Exosome miR-20a-5p from IH-stimulated bEnd3 cells can promote OSA-CI by increasing HT22 cells pyroptosis through its target MFN2.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2063-2082"},"PeriodicalIF":3.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intraoperative Sleep Spindle Activity and Postoperative Sleep Disturbance in Elderly Patients Undergoing Orthopedic Surgery: A Prospective Cohort Study.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S486625
Yuchen Dai, Kaikai Shi, Qingren Liu, Changli Shen, Xinjian Lu, Xiaodong Qiu, Jie Sun

Purpose: This study aimed to investigate the relationship between intraoperative sleep spindle activity and postoperative sleep disturbance (PSD) in elderly orthopedic surgery patients.

Patients and methods: In this prospective observational cohort study, we collected intraoperative electroencephalography (EEG) data from 212 elderly patients undergoing orthopedic surgery from May 2023 to December 2023. We used the Athens Insomnia Scale to assess sleep quality on postoperative day (POD) 1 and POD 3 and analyzed the correlation between intraoperative sleep spindle activity and PSD through logistic regression.

Results: The incidence of PSD was 65.6% on POD 1 and 41.9% on POD 3. On the first day, there were no significant differences in intraoperative sleep spindle characteristics between PSD and non-postoperative sleep disturbance (non-PSD) patients. However, by the third day, PSD patients showed lower sigma power compared to non-PSD patients, as well as lower spindle density in the bilateral frontopolar (Fp1/Fp2) and bilateral temporal (F7/F8) channels, with shorter average spindle duration (P < 0.05). Multivariate logistic regression analysis suggested that the average spindle density in F7/F8 channels (OR 0.543, 95% CI 0.375-0.786; P = 0.001) was an independent risk factor for PSD on POD 3. Furthermore, Mini-Mental State Examination (MMSE) could independently predict PSD on POD 1 (OR 0.806, 95% CI 0.656-0.991; P = 0.041) and POD 3 (OR 0.701, 95% CI 0.562-0.875; P = 0.002). Pain on movement and at rest were independently associated with PSD on POD 1 (OR 1.480, 95% CI 1.200-1.824; P < 0.001) and POD 3 (OR 1.848, 95% CI 1.166-2.927; P = 0.009), respectively.

Conclusion: Intraoperative mean spindle density in the F7/F8 channels was an independent risk factor for PSD on POD 3 in elderly patients undergoing orthopedic surgery. MMSE and postoperative pain also independently increased the risk of PSD.

{"title":"Intraoperative Sleep Spindle Activity and Postoperative Sleep Disturbance in Elderly Patients Undergoing Orthopedic Surgery: A Prospective Cohort Study.","authors":"Yuchen Dai, Kaikai Shi, Qingren Liu, Changli Shen, Xinjian Lu, Xiaodong Qiu, Jie Sun","doi":"10.2147/NSS.S486625","DOIUrl":"10.2147/NSS.S486625","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the relationship between intraoperative sleep spindle activity and postoperative sleep disturbance (PSD) in elderly orthopedic surgery patients.</p><p><strong>Patients and methods: </strong>In this prospective observational cohort study, we collected intraoperative electroencephalography (EEG) data from 212 elderly patients undergoing orthopedic surgery from May 2023 to December 2023. We used the Athens Insomnia Scale to assess sleep quality on postoperative day (POD) 1 and POD 3 and analyzed the correlation between intraoperative sleep spindle activity and PSD through logistic regression.</p><p><strong>Results: </strong>The incidence of PSD was 65.6% on POD 1 and 41.9% on POD 3. On the first day, there were no significant differences in intraoperative sleep spindle characteristics between PSD and non-postoperative sleep disturbance (non-PSD) patients. However, by the third day, PSD patients showed lower sigma power compared to non-PSD patients, as well as lower spindle density in the bilateral frontopolar (Fp1/Fp2) and bilateral temporal (F7/F8) channels, with shorter average spindle duration (<i>P</i> < 0.05). Multivariate logistic regression analysis suggested that the average spindle density in F7/F8 channels (OR 0.543, 95% CI 0.375-0.786; <i>P</i> = 0.001) was an independent risk factor for PSD on POD 3. Furthermore, Mini-Mental State Examination (MMSE) could independently predict PSD on POD 1 (OR 0.806, 95% CI 0.656-0.991; <i>P</i> = 0.041) and POD 3 (OR 0.701, 95% CI 0.562-0.875; <i>P</i> = 0.002). Pain on movement and at rest were independently associated with PSD on POD 1 (OR 1.480, 95% CI 1.200-1.824; <i>P</i> < 0.001) and POD 3 (OR 1.848, 95% CI 1.166-2.927; <i>P</i> = 0.009), respectively.</p><p><strong>Conclusion: </strong>Intraoperative mean spindle density in the F7/F8 channels was an independent risk factor for PSD on POD 3 in elderly patients undergoing orthopedic surgery. MMSE and postoperative pain also independently increased the risk of PSD.</p>","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2083-2097"},"PeriodicalIF":3.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Chronic Intermittent Hypoxia on Cognitive Function and Hippocampal Neurons in Mice: A Study of Inflammatory and Oxidative Stress Pathways.
IF 3 2区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-12-16 eCollection Date: 2024-01-01 DOI: 10.2147/NSS.S489232
Kai Zhang, Dandi Ma, Yunxiao Wu, Zhifei Xu
<p><strong>Purpose: </strong>Chronic intermittent hypoxia (CIH) is considered one of the main pathophysiological mechanisms of obstructive sleep apnea (OSA). CIH can further lead to cognitive dysfunction by inducing processes such as neuroinflammation and oxidative stress. The hippocampus is primarily associated with cognitive functions such as learning and memory. This study aimed to explore the effects of CIH on cognitive function and hippocampal neurons in mice and to reveal its potential molecular mechanisms.</p><p><strong>Methods: </strong>SPF-grade C57BL/6J mice (n=36) were selected as subjects and divided into control, mild CIH, and severe CIH groups (12 mice per group). Cognitive function was assessed using the Morris water maze test, and hippocampal neuron numbers and morphological changes were observed using HE staining and Nissl staining. Additionally, differential genes and pathways were revealed through RNA sequencing (RNA-seq) and bioinformatics analysis. We examined oxidative stress-related biochemical markers in the hippocampal tissue and used Western Blot to verify changes in the expression of potential key genes. Statistical analyses were performed using ANOVA and post hoc tests to ensure robust comparisons between groups.</p><p><strong>Results: </strong>CIH mice exhibited significant cognitive impairment, including decreased learning and memory abilities. The severe CIH group had a longer escape latency compared to the mild CIH group (p < 0.001) and the control group (p < 0.01), while the mild CIH group took longer than the control group (p < 0.01). In the probe test, the severe CIH group showed a significant decrease in platform crossings (p < 0.01) and target quadrant dwell time (p < 0.05), while the mild CIH group exhibited a reduction in target quadrant dwell time (p < 0.05). Abnormal hippocampal neuron morphology was observed, with a significant reduction in hippocampal neurons (p < 0.05). RNA-seq analysis revealed numerous differentially expressed genes, mainly enriched in biological processes such as inflammation and oxidative stress, as well as multiple signaling pathways. Specifically, downregulated LepR, SIRT1, and Nrf2 genes were found to exacerbate oxidative stress and neuroinflammation, impairing neuronal integrity and cognitive function. Further validation showed increased oxidative stress levels in hippocampal tissue and downregulation of key gene expression. Western blot analysis confirmed significantly reduced expression of LepR (p < 0.01), SIRT1 (p < 0.001), and Nrf2 (p < 0.001) in the severe CIH group.</p><p><strong>Conclusion: </strong>While oxidative stress and inflammation are well-established mechanisms in CIH-induced cognitive impairment, our study provides novel insights by identifying the specific roles of LepR, SIRT1, and Nrf2 in this process. The downregulation of these key genes suggests potential new targets for therapeutic intervention. Importantly, the differential expression patterns observed in
{"title":"Impact of Chronic Intermittent Hypoxia on Cognitive Function and Hippocampal Neurons in Mice: A Study of Inflammatory and Oxidative Stress Pathways.","authors":"Kai Zhang, Dandi Ma, Yunxiao Wu, Zhifei Xu","doi":"10.2147/NSS.S489232","DOIUrl":"10.2147/NSS.S489232","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Chronic intermittent hypoxia (CIH) is considered one of the main pathophysiological mechanisms of obstructive sleep apnea (OSA). CIH can further lead to cognitive dysfunction by inducing processes such as neuroinflammation and oxidative stress. The hippocampus is primarily associated with cognitive functions such as learning and memory. This study aimed to explore the effects of CIH on cognitive function and hippocampal neurons in mice and to reveal its potential molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;SPF-grade C57BL/6J mice (n=36) were selected as subjects and divided into control, mild CIH, and severe CIH groups (12 mice per group). Cognitive function was assessed using the Morris water maze test, and hippocampal neuron numbers and morphological changes were observed using HE staining and Nissl staining. Additionally, differential genes and pathways were revealed through RNA sequencing (RNA-seq) and bioinformatics analysis. We examined oxidative stress-related biochemical markers in the hippocampal tissue and used Western Blot to verify changes in the expression of potential key genes. Statistical analyses were performed using ANOVA and post hoc tests to ensure robust comparisons between groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CIH mice exhibited significant cognitive impairment, including decreased learning and memory abilities. The severe CIH group had a longer escape latency compared to the mild CIH group (p &lt; 0.001) and the control group (p &lt; 0.01), while the mild CIH group took longer than the control group (p &lt; 0.01). In the probe test, the severe CIH group showed a significant decrease in platform crossings (p &lt; 0.01) and target quadrant dwell time (p &lt; 0.05), while the mild CIH group exhibited a reduction in target quadrant dwell time (p &lt; 0.05). Abnormal hippocampal neuron morphology was observed, with a significant reduction in hippocampal neurons (p &lt; 0.05). RNA-seq analysis revealed numerous differentially expressed genes, mainly enriched in biological processes such as inflammation and oxidative stress, as well as multiple signaling pathways. Specifically, downregulated LepR, SIRT1, and Nrf2 genes were found to exacerbate oxidative stress and neuroinflammation, impairing neuronal integrity and cognitive function. Further validation showed increased oxidative stress levels in hippocampal tissue and downregulation of key gene expression. Western blot analysis confirmed significantly reduced expression of LepR (p &lt; 0.01), SIRT1 (p &lt; 0.001), and Nrf2 (p &lt; 0.001) in the severe CIH group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;While oxidative stress and inflammation are well-established mechanisms in CIH-induced cognitive impairment, our study provides novel insights by identifying the specific roles of LepR, SIRT1, and Nrf2 in this process. The downregulation of these key genes suggests potential new targets for therapeutic intervention. Importantly, the differential expression patterns observed in","PeriodicalId":18896,"journal":{"name":"Nature and Science of Sleep","volume":"16 ","pages":"2029-2043"},"PeriodicalIF":3.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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