癫痫与睡眠障碍相关机制研究进展_Journal of Epilepsy

Authors：

韩飞飞 ¹ , 雒晨宇 ¹ ,  孙美珍 ²

1. ;
2. ;

Corresponding author：

孙美珍, Email: sunmeizhen213@126.com

Keywords：

癫痫; 睡眠; 神经递质

DOI：

10.7507/2096-0247.202211002

Video：

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Abstract Full text Figures/Tables Video References Cited by

睡眠在癫痫疾病管理中具有非常重要的作用，睡眠的昼夜节律可以影响癫痫的发作频率及发作时间。睡眠质量下降是癫痫发作的常见诱因，提高睡眠效率和控制癫痫发作对所有癫痫患者的生活质量都有显著积极影响。癫痫发作过程机制复杂，目前研究表明癫痫发作时细胞兴奋性及一系列的神经递质、激素、离子通道发生变化，这些变化可能会作用于睡眠-觉醒周期，引发睡眠结构及昼夜节律发生变化。而这些关联可能为针对癫痫控制及癫痫患者睡眠障碍和昼夜节律紊乱提供新的治疗途径，从而达到既能良好的控制癫痫发作，又能改善患者的睡眠，从而改善患者生活质量。

Citation： 韩飞飞, 雒晨宇, 孙美珍. 癫痫与睡眠障碍相关机制研究进展. Journal of Epilepsy, 2023, 9(2): 151-155. doi: 10.7507/2096-0247.202211002 Copy

1.	Grigg-Damberger M, Foldvary-Schaefer N. Bidirectional relationships of sleep and epilepsy in adults with epilepsy. Epilepsy Behav, 2021, 116: 107735.
2.	Dehghani M, Fayyazi A, Cheraghi F, et al. The relationship between severity of epilepsy and sleep disorder in epileptic children. Iran J Child Neurol, 2019, 13(2): 77-88.
3.	Maganti RK, Jones MV. Untangling a web: basic mechanisms of the complex interactions between sleep, circadian rhythms, and epilepsy. Epilepsy Curr, 2021, 21(2): 105-110.
4.	Daley JT, DeWolfe JL. Sleep, circadian rhythms, and epilepsy. Curr Treat Options Neurol, 2018, 20(11): 47.
5.	Jain SV, Glauser TA. Effects of epilepsy treatments on sleep architecture and daytime sleepiness: an evidence-based review of objective sleep metrics. Epilepsia, 2014, 55(1): 26-37.
6.	Scarlatelli-Lima AV, Sukys-Claudino L, Watanabe N, et al. How do people with drug-resistant mesial temporal lobe epilepsy sleep? A clinical and video-EEG with EOG and submental EMG for sleep staging study. eNeurologicalSci, 2016, 4: 34-41.
7.	Yeh WC, Lai CL, Wu MN, et al. Rapid eye movement sleep disturbance in patients with refractory epilepsy: a polysomnographic study. Sleep Med, 2021, 81: 101-108.
8.	Winsor AA, Richards C, Bissell S, et al. Sleep disruption in children and adolescents with epilepsy: a systematic review and meta-analysis. Sleep Med Rev, 2021, 57: 101416.
9.	Bazil CW, Short D, Crispin D, et al. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology, 2000, 55(11): 1746-1748.
10.	de Lima E, Soares JM Jr, del Carmen Sanabria Garrido Y, et al. Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats. Brain Res, 2005, 1043(1-2): 24-31.
11.	Ko GY, Shi L, Ko ML. Circadian regulation of ion channels and their functions. J Neurochem, 2009, 110(4): 1150-1169.
12.	Herman ST, Walczak TS, Bazil CW. Distribution of partial seizures during the sleep-wake cycle: differences by seizure onset site. Neurology, 2001, 56(11): 1453-1459.
13.	Unterberger I, Gabelia D, Prieschl M, et al. Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study. Sleep Med, 2015, 16(2): 237-242.
14.	Anaclet C, Ferrari L, Arrigoni E, et al. The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. Nat Neurosci, 2014, 17(9): 1217-1224.
15.	Chung S, Weber F, Zhong P, et al. Identification of preoptic sleep neurons using retrograde labelling and gene profiling. Nature, 2017, 545(7655): 477-481.
16.	Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature, 2005, 437(7063): 1257-1263.
17.	Liu K, Kim J, Kim DW, et al. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature, 2017, 548(7669): 582-587.
18.	Yamatsu A, Yamashita Y, Pandharipande T, et al. Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans. Food Sci Biotechnol, 2016, 25(2): 547-551.
19.	Hong KB, Park Y, Suh HJ. Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models. Behav Brain Res, 2016, 310: 36-41.
20.	Chen X, Jia X, Zhang Y, et al. The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice. Ann Palliat Med, 2021, 10(10): 11074-11082.
21.	Riaz M, Abbasi MH, Sheikh N, et al. GABRA1 and GABRA6 gene mutations in idiopathic generalized epilepsy patients. Seizure, 2021, 93: 88-94.
22.	Meyerhoff DJ, Mon A, Metzler T, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep, 2014, 37(5): 893-900.
23.	Smirnova EY, Chizhov AV, Zaitsev AV. Presynaptic GABAB receptors underlie the antiepileptic effect of low-frequency electrical stimulation in the 4-aminopyridine model of epilepsy in brain slices of young rats. Brain Stimul, 2020, 13(5): 1387-1395.
24.	Jones BE. From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci, 2005, 26(11): 578-586.
25.	Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron, 2017, 93(4): 747-765.
26.	杨燕飞, 黄志力. 特异性控制神经元活性法研究睡眠-觉醒机制新进展. 神经药理学报, 2018, 8(1): 23-34.
27.	钟明奎, 赵乐章, 张瑾, 等. 海马微量注射乙酰胆碱和阿托品对大鼠睡眠的影响. 中国中医基础医学杂志, 2002, 8(1): 9-10.
28.	Ni KM, Hou XJ, Yang CH, et al. Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. Elife, 2016, 5: e10382.
29.	Dai X, Zhou E, Yang W, et al. Molecular resolution of a behavioral paradox: sleep and arousal are regulated by distinct acetylcholine receptors in different neuronal types in Drosophila. Sleep, 2021, 44(7): zsab017.
30.	Weltzin MM, George AA, Lukas RJ, et al. Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4β2- nicotinic acetylcholine receptor intracellular structures. PLoS One, 2021, 16(3): e0247825.
31.	Gigout S, Wierschke S, Dehnicke C, et al. Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(5): 487-496.
32.	Burgess HJ, Emens JS. Circadian-based therapies for circadian rhythm sleep-wake disorders. Curr Sleep Med Rep, 2016, 2(3): 158-165.
33.	Niu L, Li Y, Zong P, et al. Melatonin promotes sleep by activating the BK channel in C. elegans. Proc Natl Acad Sci U S A, 2020, 117(40): 25128-25137.
34.	Iyer KK, Zalesky A, Cocchi L, et al. Neural correlates of sleep recovery following melatonin treatment for pediatric concussion: a randomized controlled trial. J Neurotrauma, 2020, 37(24): 2647-2655.
35.	Jia X, Zhang L, Zhang W, et al. Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice. Basic Clin Pharmacol Toxicol, 2021, 128(2): 256-267.
36.	Jafari-Koulaee A, Bagheri-Nesami M. The effect of melatonin on sleep quality and insomnia in patients with cancer: a systematic review study. Sleep Med, 2021, 82: 96-103.
37.	Schapel GJ, Beran RG, Kennaway DL, et al. Melatonin response in active epilepsy. Epilepsia, 1995, 36(1): 75-78.
38.	Molina-Carballo A, Muñoz-Hoyos A, Sánchez-Forte M, et al. Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics, 2007, 38(3): 122-125.
39.	郭静芳, 姚宝珍. 癫癎和热性惊厥患儿血清褪黑素水平的变化及其临床意义. 中国当代儿科杂志, 2009, 11(04): 288-290.
40.	Yalýn O, Arman F, Erdoğan F, et al. A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav, 2006, 8(3): 542-546.
41.	Ayça S, Aksoy HU, Taştan İ, et al. Levels of melatonin in continuous spikes and waves during sleep. J Child Neurol, 2019, 34(6): 309-312.
42.	Ma Y, Sun X, Li J, et al. Melatonin alleviates the epilepsy-associated impairments in hippocampal LTP and spatial learning through rescue of surface GluR2 expression at hippocampal CA1 synapses. Neurochem Res, 2017, 42(5): 1438-1448.
43.	Jagannath A, Varga N, Dallmann R, et al. Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nat Commun, 2021, 12(1): 2113.
44.	Boison D, Aronica E. Comorbidities in neurology: is adenosine the common link? Neuropharmacology, 2015, 97: 18-34.
45.	Masino SA, Li T, Theofilas P, et al. A ketogenic diet suppresses seizures in mice through adenosine A1 receptors. J Clin Invest, 2011, 121(7): 2679-2683.
46.	Warren TJ, Simeone TA, Smith DD, et al. Adenosine has two faces: regionally dichotomous adenosine tone in a model of epilepsy with comorbid sleep disorders. Neurobiol Dis, 2018, 114: 45-52.
47.	Li R, Wang YQ, Liu WY, et al. Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents. Neuropharmacology, 2020, 168: 107923.
48.	Wang YQ, Li R, Wang DR, et al. Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents. Brain Struct Funct, 2017, 222(3): 1351-1366.
49.	Zhou X, Oishi Y, Cherasse Y, et al. Extracellular adenosine and slow-wave sleep are increased after ablation of nucleus accumbens core astrocytes and neurons in mice. Neurochem Int, 2019, 124: 256-263.
50.	Carley DW, Trbovic SM, Radulovacki M. Diazepam suppresses sleep apneas in rats. Am J Respir Crit Care Med, 1998, 157(3): 917-920.
51.	张小军, 徐建芳. 左乙拉西坦递增疗法对局灶性癫痫患儿脑神经递质及睡眠结构的影响. 实用医院临床杂志, 2021, 18(2): 156-159.
52.	Bazil CW, Dave J, Cole J, et al. Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav, 2012, 23(4): 422-425.
53.	Romigi A, Izzi F, Marciani MG, et al. Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study. Eur J Neurol, 2009, 16(1): 70-75.
54.	Ayala-Guerrero F, Mexicano G, Gutiérrez-Chávez CA, et al. Effect of gabapentin on sleep patterns disturbed by epilepsy. Epilepsy Behav, 2019, 92: 290-296.
55.	Zhang H, Li Y, Li X, et al. Effect of sodium valproate on the sleep structures of epileptic patients. Exp Ther Med, 2014, 7(5): 1227-1232.
56.	Liu J, Clough SJ, Hutchinson AJ, et al. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol, 2016, 56(1): 361-383.
57.	Muehlan C, Vaillant C, Zenklusen I, et al. Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders. Expert Opin Drug Metab Toxicol, 2020, 16(11): 1063-1078.
58.	Gizowski C, Bourque CW. Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature, 2020, 583(7816): 421-424.

1. Grigg-Damberger M, Foldvary-Schaefer N. Bidirectional relationships of sleep and epilepsy in adults with epilepsy. Epilepsy Behav, 2021, 116: 107735.
2. Dehghani M, Fayyazi A, Cheraghi F, et al. The relationship between severity of epilepsy and sleep disorder in epileptic children. Iran J Child Neurol, 2019, 13(2): 77-88.
3. Maganti RK, Jones MV. Untangling a web: basic mechanisms of the complex interactions between sleep, circadian rhythms, and epilepsy. Epilepsy Curr, 2021, 21(2): 105-110.
4. Daley JT, DeWolfe JL. Sleep, circadian rhythms, and epilepsy. Curr Treat Options Neurol, 2018, 20(11): 47.
5. Jain SV, Glauser TA. Effects of epilepsy treatments on sleep architecture and daytime sleepiness: an evidence-based review of objective sleep metrics. Epilepsia, 2014, 55(1): 26-37.
6. Scarlatelli-Lima AV, Sukys-Claudino L, Watanabe N, et al. How do people with drug-resistant mesial temporal lobe epilepsy sleep? A clinical and video-EEG with EOG and submental EMG for sleep staging study. eNeurologicalSci, 2016, 4: 34-41.
7. Yeh WC, Lai CL, Wu MN, et al. Rapid eye movement sleep disturbance in patients with refractory epilepsy: a polysomnographic study. Sleep Med, 2021, 81: 101-108.
8. Winsor AA, Richards C, Bissell S, et al. Sleep disruption in children and adolescents with epilepsy: a systematic review and meta-analysis. Sleep Med Rev, 2021, 57: 101416.
9. Bazil CW, Short D, Crispin D, et al. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology, 2000, 55(11): 1746-1748.
10. de Lima E, Soares JM Jr, del Carmen Sanabria Garrido Y, et al. Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats. Brain Res, 2005, 1043(1-2): 24-31.
11. Ko GY, Shi L, Ko ML. Circadian regulation of ion channels and their functions. J Neurochem, 2009, 110(4): 1150-1169.
12. Herman ST, Walczak TS, Bazil CW. Distribution of partial seizures during the sleep-wake cycle: differences by seizure onset site. Neurology, 2001, 56(11): 1453-1459.
13. Unterberger I, Gabelia D, Prieschl M, et al. Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study. Sleep Med, 2015, 16(2): 237-242.
14. Anaclet C, Ferrari L, Arrigoni E, et al. The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. Nat Neurosci, 2014, 17(9): 1217-1224.
15. Chung S, Weber F, Zhong P, et al. Identification of preoptic sleep neurons using retrograde labelling and gene profiling. Nature, 2017, 545(7655): 477-481.
16. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature, 2005, 437(7063): 1257-1263.
17. Liu K, Kim J, Kim DW, et al. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature, 2017, 548(7669): 582-587.
18. Yamatsu A, Yamashita Y, Pandharipande T, et al. Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans. Food Sci Biotechnol, 2016, 25(2): 547-551.
19. Hong KB, Park Y, Suh HJ. Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models. Behav Brain Res, 2016, 310: 36-41.
20. Chen X, Jia X, Zhang Y, et al. The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice. Ann Palliat Med, 2021, 10(10): 11074-11082.
21. Riaz M, Abbasi MH, Sheikh N, et al. GABRA1 and GABRA6 gene mutations in idiopathic generalized epilepsy patients. Seizure, 2021, 93: 88-94.
22. Meyerhoff DJ, Mon A, Metzler T, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep, 2014, 37(5): 893-900.
23. Smirnova EY, Chizhov AV, Zaitsev AV. Presynaptic GABAB receptors underlie the antiepileptic effect of low-frequency electrical stimulation in the 4-aminopyridine model of epilepsy in brain slices of young rats. Brain Stimul, 2020, 13(5): 1387-1395.
24. Jones BE. From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci, 2005, 26(11): 578-586.
25. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron, 2017, 93(4): 747-765.
26. 杨燕飞, 黄志力. 特异性控制神经元活性法研究睡眠-觉醒机制新进展. 神经药理学报, 2018, 8(1): 23-34.
27. 钟明奎, 赵乐章, 张瑾, 等. 海马微量注射乙酰胆碱和阿托品对大鼠睡眠的影响. 中国中医基础医学杂志, 2002, 8(1): 9-10.
28. Ni KM, Hou XJ, Yang CH, et al. Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. Elife, 2016, 5: e10382.
29. Dai X, Zhou E, Yang W, et al. Molecular resolution of a behavioral paradox: sleep and arousal are regulated by distinct acetylcholine receptors in different neuronal types in Drosophila. Sleep, 2021, 44(7): zsab017.
30. Weltzin MM, George AA, Lukas RJ, et al. Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4β2- nicotinic acetylcholine receptor intracellular structures. PLoS One, 2021, 16(3): e0247825.
31. Gigout S, Wierschke S, Dehnicke C, et al. Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(5): 487-496.
32. Burgess HJ, Emens JS. Circadian-based therapies for circadian rhythm sleep-wake disorders. Curr Sleep Med Rep, 2016, 2(3): 158-165.
33. Niu L, Li Y, Zong P, et al. Melatonin promotes sleep by activating the BK channel in C. elegans. Proc Natl Acad Sci U S A, 2020, 117(40): 25128-25137.
34. Iyer KK, Zalesky A, Cocchi L, et al. Neural correlates of sleep recovery following melatonin treatment for pediatric concussion: a randomized controlled trial. J Neurotrauma, 2020, 37(24): 2647-2655.
35. Jia X, Zhang L, Zhang W, et al. Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice. Basic Clin Pharmacol Toxicol, 2021, 128(2): 256-267.
36. Jafari-Koulaee A, Bagheri-Nesami M. The effect of melatonin on sleep quality and insomnia in patients with cancer: a systematic review study. Sleep Med, 2021, 82: 96-103.
37. Schapel GJ, Beran RG, Kennaway DL, et al. Melatonin response in active epilepsy. Epilepsia, 1995, 36(1): 75-78.
38. Molina-Carballo A, Muñoz-Hoyos A, Sánchez-Forte M, et al. Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics, 2007, 38(3): 122-125.
39. 郭静芳, 姚宝珍. 癫癎和热性惊厥患儿血清褪黑素水平的变化及其临床意义. 中国当代儿科杂志, 2009, 11(04): 288-290.
40. Yalýn O, Arman F, Erdoğan F, et al. A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav, 2006, 8(3): 542-546.
41. Ayça S, Aksoy HU, Taştan İ, et al. Levels of melatonin in continuous spikes and waves during sleep. J Child Neurol, 2019, 34(6): 309-312.
42. Ma Y, Sun X, Li J, et al. Melatonin alleviates the epilepsy-associated impairments in hippocampal LTP and spatial learning through rescue of surface GluR2 expression at hippocampal CA1 synapses. Neurochem Res, 2017, 42(5): 1438-1448.
43. Jagannath A, Varga N, Dallmann R, et al. Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nat Commun, 2021, 12(1): 2113.
44. Boison D, Aronica E. Comorbidities in neurology: is adenosine the common link? Neuropharmacology, 2015, 97: 18-34.
45. Masino SA, Li T, Theofilas P, et al. A ketogenic diet suppresses seizures in mice through adenosine A1 receptors. J Clin Invest, 2011, 121(7): 2679-2683.
46. Warren TJ, Simeone TA, Smith DD, et al. Adenosine has two faces: regionally dichotomous adenosine tone in a model of epilepsy with comorbid sleep disorders. Neurobiol Dis, 2018, 114: 45-52.
47. Li R, Wang YQ, Liu WY, et al. Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents. Neuropharmacology, 2020, 168: 107923.
48. Wang YQ, Li R, Wang DR, et al. Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents. Brain Struct Funct, 2017, 222(3): 1351-1366.
49. Zhou X, Oishi Y, Cherasse Y, et al. Extracellular adenosine and slow-wave sleep are increased after ablation of nucleus accumbens core astrocytes and neurons in mice. Neurochem Int, 2019, 124: 256-263.
50. Carley DW, Trbovic SM, Radulovacki M. Diazepam suppresses sleep apneas in rats. Am J Respir Crit Care Med, 1998, 157(3): 917-920.
51. 张小军, 徐建芳. 左乙拉西坦递增疗法对局灶性癫痫患儿脑神经递质及睡眠结构的影响. 实用医院临床杂志, 2021, 18(2): 156-159.
52. Bazil CW, Dave J, Cole J, et al. Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav, 2012, 23(4): 422-425.
53. Romigi A, Izzi F, Marciani MG, et al. Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study. Eur J Neurol, 2009, 16(1): 70-75.
54. Ayala-Guerrero F, Mexicano G, Gutiérrez-Chávez CA, et al. Effect of gabapentin on sleep patterns disturbed by epilepsy. Epilepsy Behav, 2019, 92: 290-296.
55. Zhang H, Li Y, Li X, et al. Effect of sodium valproate on the sleep structures of epileptic patients. Exp Ther Med, 2014, 7(5): 1227-1232.
56. Liu J, Clough SJ, Hutchinson AJ, et al. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol, 2016, 56(1): 361-383.
57. Muehlan C, Vaillant C, Zenklusen I, et al. Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders. Expert Opin Drug Metab Toxicol, 2020, 16(11): 1063-1078.
58. Gizowski C, Bourque CW. Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature, 2020, 583(7816): 421-424.

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