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Биоэлектрическая активность мозга у женщин со склерозирующим лихеном вульвы
Биоэлектрическая активность мозга у женщин со склерозирующим лихеном вульвы
Логинов В.В., Вартанов А.В., Фейгин С.А. и др. Биоэлектрическая активность мозга у женщин со склерозирующим лихеном вульвы. Гинекология. 2020; 22 (6): 68–73. DOI: 10.26442/20795696.2020.6.200466
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Аннотация
Цель. Изучить особенности биоэлектрической активности головного мозга пациенток со склерозирующим лихеном вульвы (СЛВ). Определить взаимосвязь между иммунной системой и центральной нервной системой, структурами головного мозга и основными симптомами СЛВ.
Материалы и методы. 102 пациентки с СЛВ в возрасте 21–78 лет (средний возраст –50,57±13,92 года) опрошены о качестве сна и наличии фобий. Из них 30 пациенткам в возрасте 21–72 лет (средний возраст – 46,07±15,42 года) после подписания информированного согласия проведена электроэнцефалография (ЭЭГ). Критерием включения служил СЛВ в стадии обострения, подтвержденный гистологическим исследованием.
Результаты. Среди жалоб значимым отмечен только зуд наружных половых органов и/или во влагалище, коррелирующий с системными изменениями мозговой активности и взаимосвязанный с такими структурами, как ствол мозга и бледный шар, вентральный стриатум, островок, париетальная кора, поле 40 по Бродману (супрамаргинальная извилина), а также области первичной зрительной коры (поле 17 по Бродману).
Заключение. СЛВ чаще сопровождается зудом наружных половых органов (73,3%) и имеет средний показатель 5,6 балла по 10-балльной шкале. При длительности заболевания 6 лет и более и уровне интенсивности зуда 5–6 баллов и выше могут быть рекомендованы консультация невролога и проведение ЭЭГ. Основной особенностью биоэлектрической активности при СЛВ является наличие признаков органического поражения головного мозга. Заболевание сопровождается нарушением висцеральных регуляторных механизмов головного мозга, что приводит к формированию низкокомплементарного «висцерома» и нейродегенеративных признаков на ЭЭГ. Частое сочетание нарушений в центральной нервной и иммунной системе дает основание рассматривать СЛВ в рамках синдрома хронической усталости.
Ключевые слова: склерозирующий лихен вульвы, биоэлектрическая активность мозга, электроэнцефалографическое исследование.
Materials and methods. 102 patients aged 21 to 78 years (average age 50.57±13.92 years) were questioned about the VLS symptoms, the quality of sleep and presence of phobias, of which 30 patients aged 21 to 72 years (average age 46.07±15.42 years) after signing informed consent underwent electroencephalographic (EEG) study. Inclusion criteria were patients aged 18 and older, vulvar lichen sclerosus in the acute stage, confirmed by histological examination.
Results. The common complaint was itching in external genitalia (73.3%), which was statistically evident in the analysis of brain activity. Itching of external genitalia in patients with VLS could account for systemic changes in the activity and interactions of such structures as the brain stem and globus pallidus, ventral striatum, islet, parietal cortex, field 40 according to Broadman (supramarginal gyrus), as well as areas of the primary visual cortex (field 17 according to Broadman).
Conclusion. VLS is often accompanied by itching in the external genitalia (73.3%), and has an average score of 5.6 on a ten-point scale. EEG is recommended with a disease duration of more than 6 years and an itch level of 5–6 points or more. The main feature of brain bioelectric activity in patients with VLS is evident signs of organic brain damage. The disease is accompanied by impairment of the visceral regulatory mechanisms of the brain, which leads to the formation of a low-complementary “viscerom” and neurodegenerative signs in the EEG. A frequent combination of disorders in the central nervous system and immune system gives reason to consider VLS associated with chronic fatigue syndrome.
Key words: vulvar lichen sclerosus, bioelectric activity of the brain, electroencephalographic study.
Материалы и методы. 102 пациентки с СЛВ в возрасте 21–78 лет (средний возраст –50,57±13,92 года) опрошены о качестве сна и наличии фобий. Из них 30 пациенткам в возрасте 21–72 лет (средний возраст – 46,07±15,42 года) после подписания информированного согласия проведена электроэнцефалография (ЭЭГ). Критерием включения служил СЛВ в стадии обострения, подтвержденный гистологическим исследованием.
Результаты. Среди жалоб значимым отмечен только зуд наружных половых органов и/или во влагалище, коррелирующий с системными изменениями мозговой активности и взаимосвязанный с такими структурами, как ствол мозга и бледный шар, вентральный стриатум, островок, париетальная кора, поле 40 по Бродману (супрамаргинальная извилина), а также области первичной зрительной коры (поле 17 по Бродману).
Заключение. СЛВ чаще сопровождается зудом наружных половых органов (73,3%) и имеет средний показатель 5,6 балла по 10-балльной шкале. При длительности заболевания 6 лет и более и уровне интенсивности зуда 5–6 баллов и выше могут быть рекомендованы консультация невролога и проведение ЭЭГ. Основной особенностью биоэлектрической активности при СЛВ является наличие признаков органического поражения головного мозга. Заболевание сопровождается нарушением висцеральных регуляторных механизмов головного мозга, что приводит к формированию низкокомплементарного «висцерома» и нейродегенеративных признаков на ЭЭГ. Частое сочетание нарушений в центральной нервной и иммунной системе дает основание рассматривать СЛВ в рамках синдрома хронической усталости.
Ключевые слова: склерозирующий лихен вульвы, биоэлектрическая активность мозга, электроэнцефалографическое исследование.
________________________________________________
Materials and methods. 102 patients aged 21 to 78 years (average age 50.57±13.92 years) were questioned about the VLS symptoms, the quality of sleep and presence of phobias, of which 30 patients aged 21 to 72 years (average age 46.07±15.42 years) after signing informed consent underwent electroencephalographic (EEG) study. Inclusion criteria were patients aged 18 and older, vulvar lichen sclerosus in the acute stage, confirmed by histological examination.
Results. The common complaint was itching in external genitalia (73.3%), which was statistically evident in the analysis of brain activity. Itching of external genitalia in patients with VLS could account for systemic changes in the activity and interactions of such structures as the brain stem and globus pallidus, ventral striatum, islet, parietal cortex, field 40 according to Broadman (supramarginal gyrus), as well as areas of the primary visual cortex (field 17 according to Broadman).
Conclusion. VLS is often accompanied by itching in the external genitalia (73.3%), and has an average score of 5.6 on a ten-point scale. EEG is recommended with a disease duration of more than 6 years and an itch level of 5–6 points or more. The main feature of brain bioelectric activity in patients with VLS is evident signs of organic brain damage. The disease is accompanied by impairment of the visceral regulatory mechanisms of the brain, which leads to the formation of a low-complementary “viscerom” and neurodegenerative signs in the EEG. A frequent combination of disorders in the central nervous system and immune system gives reason to consider VLS associated with chronic fatigue syndrome.
Key words: vulvar lichen sclerosus, bioelectric activity of the brain, electroencephalographic study.
Полный текст
Список литературы
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4. Marfatia Y, Surani A, Baxi R. Genital lichen sclerosus et atrophicus in females: an update. Indian J Sex Transm Dis AIDS 2019; 40 (1): 6–12. DOI: 10.4103/ijstd.IJSTD_23_19
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6. Аполихина И.А., Соколова А.В. Лечение склерозирующего лихена вульвы: от стандартов к инновациям. Акушерство и гинекология. 2020; 8.
[Apolikhina I.A., Sokolova A.V. Lechenie skleroziruiushchego likhena vul'vy: ot standartov k innovatsiiam. Akusherstvo i ginekologiia. 2020; 8 (in Russian).]
7. Tran DA, Tan X, Macri CJ et al. Lichen sclerosus: an autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int J Biol Sci 2019; 15 (7): 1429–39.
8. Goldstein AT, Marinoff SC, Christopher K, Srodon M. Prevalence of vulvar lichen sclerosus in a general gynecology practice. J Reprod Med 2005; 50: 477–80.
9. Lanteaume L et al. Emotion induction after direct intracerebral stimulations of human amygdale. Cerebl Cortex 2007; 17 (6): 1307–13.
10. Swaab DF. Sexual orientation and its basis in brain structure and function. Proceedings of the National Academy of Sciences of the United States. Am J 2008; 105 (30): 10273–4. DOI:10.1073/pnas.0805542105
11. Zeki S, Romaya JP, Lauwereyns J. Neural Correlates of Hate. PLoS ONE 2008; 3 (10): e3556. DOI: 10.1371/journal.pone.0003556
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[Vіnichuk S.M., Dubenko E.G., Macheret E.L. et al. Nervovі khvorobi. K.: Zdorov'ia. 2001; 115–6 (in Ukrainian).]
16. Van der Linden C, Colle H, Vandewalle V. Successful treatment of tics with bilateral internal pallidum (GPi) stimulation in a 27-year-old male patient with Gilles de la Tourette's syndrome (GTS). Mov Disord 2002; 17 (5): 341.
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18. Dong S, Zhuang P, Zhang X-H et al. Unilateral deep brain stimulation of the right globus pallidus internus in patients with Tourette's syndrome: two cases with outcomes after 1 year and a brief review of the literature. J Int Med Res 2012; 40 (5): 2021–28.
19. Craig AD, Chen K, Bandy D, Reiman EM. Thermosensory activation of insular cortex. Nat Neurosci 2000; 3 (2): 184–90.
20. Ladabaum U, Minoshima S, Hasler WL et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology 2001; 120 (2): 369–76. http://linkinghub.elsevier.com/retrieve/pii/S0016508501699906
21. Matsuura S, Kakizaki H, Mitsui T et al. Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. J Urol 2002; 168 (5): 2035–9. http://linkinghub.elsevier.com/retrieve/pii/S0022-5347(05)64290-5
22. Hamaguchi T, Kano M, Rikimaru H et al. Brain activity during distention of the descending colon in humans. Neurogastroenterol Motil 2004; 16 (3): 299–309.
23. Olausson H, Charron J, Marchand S et al. Feelings of warmth correlate with neural activity in right anterior insular cortex. Neurosci Lett 2005; 389 (1): 1–5.
24. Song GH, Venkatraman V, Ho KY et al. Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. J Pain Symptom 2006; 126 (1–3): 79–90. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(06)00340-X
25. Sanfey AG, Rilling JK, Aronson JA et al. The neural basis of economic decision-making in the ultimatum game. Science 2003; 300 (5626): 1755–8.
26. Silani C. I'm OK, You're not OK: right supramarginal gyrus plays an important role in empathy. Sci Daily. 2013.
J Dermatol 2004; 45: 12–5.
2. Aidé S, Lattario FR, Almeida G. et al. Epstein–Barr virus and human papillomavirus infection in vulvar lichen sclerosus. J Low Genit Tract Dis 2010; 14(4): 319–22.
3. Virgili A, Borghi A, Cazzaniga S et al. GLS Italian study group. New insights into potential risk factors and associations in genital lichen sclerosus: data from a multicentre Italian study on 729 consecutive cases.
J Eur Acad Dermatol Venereol 2016; 31 (4): 699–704.
4. Marfatia Y, Surani A, Baxi R. Genital lichen sclerosus et atrophicus in females: an update. Indian J Sex Transm Dis AIDS 2019; 40 (1): 6–12. DOI: 10.4103/ijstd.IJSTD_23_19
5. Haefner HK, Welch KC, Rolston AM et al. Genomic profiling of vulvar lichen sclerosus patients shows possible pathogenetic disease mechanisms. J Low Genit Tract Dis 2019; 23 (3): 214–9.
6. Apolikhina I.A., Sokolova A.V. Lechenie skleroziruiushchego likhena vul'vy: ot standartov k innovatsiiam. Akusherstvo i ginekologiia. 2020; 8 (in Russian).
7. Tran DA, Tan X, Macri CJ et al. Lichen sclerosus: an autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int J Biol Sci 2019; 15 (7): 1429–39.
8. Goldstein AT, Marinoff SC, Christopher K, Srodon M. Prevalence of vulvar lichen sclerosus in a general gynecology practice. J Reprod Med 2005; 50: 477–80.
9. Lanteaume L et al. Emotion induction after direct intracerebral stimulations of human amygdale. Cerebl Cortex 2007; 17 (6): 1307–13.
10. Swaab DF. Sexual orientation and its basis in brain structure and function. Proceedings of the National Academy of Sciences of the United States. Am J 2008; 105 (30): 10273–4. DOI:10.1073/pnas.0805542105
11. Zeki S, Romaya JP, Lauwereyns J. Neural Correlates of Hate. PLoS ONE 2008; 3 (10): e3556. DOI: 10.1371/journal.pone.0003556
12. Volman SF, Lammel S, Margolis EB et al. New insights into the specificity and plasticity of reward and aversion encoding in the mesolimbic system. J Neurosci 2013; 33 (45): 17569–76.
13. Everitt BJ, Robbins TW. From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev 2013; 37 (9): 1946–54.
14. Hadland KA, Rushworth MF et al. The effect of cingulate lesions on social behaviour and emotion. Neuropsychologia 2003; 41 (8): 919–31. DOI: 10.1016/s0028-3932(02)00325-1
15. Vіnichuk S.M., Dubenko E.G., Macheret E.L. et al. Nervovі khvorobi. K.: Zdorov'ia. 2001; 115–6 (in Ukrainian).
16. Van der Linden C, Colle H, Vandewalle V. Successful treatment of tics with bilateral internal pallidum (GPi) stimulation in a 27-year-old male patient with Gilles de la Tourette's syndrome (GTS). Mov Disord 2002; 17 (5): 341.
17. Martínez-Fernández R, Zrinzo L, Aviles-Olmos I. Deep brain stimulation for Gilles de la Tourette syndrome: a case series targeting subregions of the globus pallidus internus. Mov Disord 2011; 26: 1922–30.
18. Dong S, Zhuang P, Zhang X-H et al. Unilateral deep brain stimulation of the right globus pallidus internus in patients with Tourette's syndrome: two cases with outcomes after 1 year and a brief review of the literature. J Int Med Res 2012; 40 (5): 2021–28.
19. Craig AD, Chen K, Bandy D, Reiman EM. Thermosensory activation of insular cortex. Nat Neurosci 2000; 3 (2): 184–90.
20. Ladabaum U, Minoshima S, Hasler WL et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology 2001; 120 (2): 369–76. http://linkinghub.elsevier.com/retrieve/pii/S0016508501699906
21. Matsuura S, Kakizaki H, Mitsui T et al. Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. J Urol 2002; 168 (5): 2035–9. http://linkinghub.elsevier.com/retrieve/pii/S0022-5347(05)64290-5
22. Hamaguchi T, Kano M, Rikimaru H et al. Brain activity during distention of the descending colon in humans. Neurogastroenterol Motil 2004; 16 (3): 299–309.
23. Olausson H, Charron J, Marchand S et al. Feelings of warmth correlate with neural activity in right anterior insular cortex. Neurosci Lett 2005; 389 (1): 1–5.
24. Song GH, Venkatraman V, Ho KY et al. Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. J Pain Symptom 2006; 126 (1–3): 79–90. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(06)00340-X
25. Sanfey AG, Rilling JK, Aronson JA et al. The neural basis of economic decision-making in the ultimatum game. Science 2003; 300 (5626): 1755–8.
26. Silani C. I'm OK, You're not OK: right supramarginal gyrus plays an important role in empathy. Sci Daily. 2013.
J Dermatol 2004; 45: 12–5.
2. Aidé S, Lattario FR, Almeida G. et al. Epstein–Barr virus and human papillomavirus infection in vulvar lichen sclerosus. J Low Genit Tract Dis 2010; 14(4): 319–22.
3. Virgili A, Borghi A, Cazzaniga S et al. GLS Italian study group. New insights into potential risk factors and associations in genital lichen sclerosus: data from a multicentre Italian study on 729 consecutive cases.
J Eur Acad Dermatol Venereol 2016; 31 (4): 699–704.
4. Marfatia Y, Surani A, Baxi R. Genital lichen sclerosus et atrophicus in females: an update. Indian J Sex Transm Dis AIDS 2019; 40 (1): 6–12. DOI: 10.4103/ijstd.IJSTD_23_19
5. Haefner HK, Welch KC, Rolston AM et al. Genomic profiling of vulvar lichen sclerosus patients shows possible pathogenetic disease mechanisms. J Low Genit Tract Dis 2019; 23 (3): 214–9.
6. Аполихина И.А., Соколова А.В. Лечение склерозирующего лихена вульвы: от стандартов к инновациям. Акушерство и гинекология. 2020; 8.
[Apolikhina I.A., Sokolova A.V. Lechenie skleroziruiushchego likhena vul'vy: ot standartov k innovatsiiam. Akusherstvo i ginekologiia. 2020; 8 (in Russian).]
7. Tran DA, Tan X, Macri CJ et al. Lichen sclerosus: an autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int J Biol Sci 2019; 15 (7): 1429–39.
8. Goldstein AT, Marinoff SC, Christopher K, Srodon M. Prevalence of vulvar lichen sclerosus in a general gynecology practice. J Reprod Med 2005; 50: 477–80.
9. Lanteaume L et al. Emotion induction after direct intracerebral stimulations of human amygdale. Cerebl Cortex 2007; 17 (6): 1307–13.
10. Swaab DF. Sexual orientation and its basis in brain structure and function. Proceedings of the National Academy of Sciences of the United States. Am J 2008; 105 (30): 10273–4. DOI:10.1073/pnas.0805542105
11. Zeki S, Romaya JP, Lauwereyns J. Neural Correlates of Hate. PLoS ONE 2008; 3 (10): e3556. DOI: 10.1371/journal.pone.0003556
12. Volman SF, Lammel S, Margolis EB et al. New insights into the specificity and plasticity of reward and aversion encoding in the mesolimbic system. J Neurosci 2013; 33 (45): 17569–76.
13. Everitt BJ, Robbins TW. From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev 2013; 37 (9): 1946–54.
14. Hadland KA, Rushworth MF et al. The effect of cingulate lesions on social behaviour and emotion. Neuropsychologia 2003; 41 (8): 919–31. DOI: 10.1016/s0028-3932(02)00325-1
15. Віничук С.М., Дубенко Є.Г., Мачерет Є.Л. та ін. Нервові хвороби. К.: Здоров'я. 2001; 115–6.
[Vіnichuk S.M., Dubenko E.G., Macheret E.L. et al. Nervovі khvorobi. K.: Zdorov'ia. 2001; 115–6 (in Ukrainian).]
16. Van der Linden C, Colle H, Vandewalle V. Successful treatment of tics with bilateral internal pallidum (GPi) stimulation in a 27-year-old male patient with Gilles de la Tourette's syndrome (GTS). Mov Disord 2002; 17 (5): 341.
17. Martínez-Fernández R, Zrinzo L, Aviles-Olmos I. Deep brain stimulation for Gilles de la Tourette syndrome: a case series targeting subregions of the globus pallidus internus. Mov Disord 2011; 26: 1922–30.
18. Dong S, Zhuang P, Zhang X-H et al. Unilateral deep brain stimulation of the right globus pallidus internus in patients with Tourette's syndrome: two cases with outcomes after 1 year and a brief review of the literature. J Int Med Res 2012; 40 (5): 2021–28.
19. Craig AD, Chen K, Bandy D, Reiman EM. Thermosensory activation of insular cortex. Nat Neurosci 2000; 3 (2): 184–90.
20. Ladabaum U, Minoshima S, Hasler WL et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology 2001; 120 (2): 369–76. http://linkinghub.elsevier.com/retrieve/pii/S0016508501699906
21. Matsuura S, Kakizaki H, Mitsui T et al. Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. J Urol 2002; 168 (5): 2035–9. http://linkinghub.elsevier.com/retrieve/pii/S0022-5347(05)64290-5
22. Hamaguchi T, Kano M, Rikimaru H et al. Brain activity during distention of the descending colon in humans. Neurogastroenterol Motil 2004; 16 (3): 299–309.
23. Olausson H, Charron J, Marchand S et al. Feelings of warmth correlate with neural activity in right anterior insular cortex. Neurosci Lett 2005; 389 (1): 1–5.
24. Song GH, Venkatraman V, Ho KY et al. Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. J Pain Symptom 2006; 126 (1–3): 79–90. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(06)00340-X
25. Sanfey AG, Rilling JK, Aronson JA et al. The neural basis of economic decision-making in the ultimatum game. Science 2003; 300 (5626): 1755–8.
26. Silani C. I'm OK, You're not OK: right supramarginal gyrus plays an important role in empathy. Sci Daily. 2013.
________________________________________________
J Dermatol 2004; 45: 12–5.
2. Aidé S, Lattario FR, Almeida G. et al. Epstein–Barr virus and human papillomavirus infection in vulvar lichen sclerosus. J Low Genit Tract Dis 2010; 14(4): 319–22.
3. Virgili A, Borghi A, Cazzaniga S et al. GLS Italian study group. New insights into potential risk factors and associations in genital lichen sclerosus: data from a multicentre Italian study on 729 consecutive cases.
J Eur Acad Dermatol Venereol 2016; 31 (4): 699–704.
4. Marfatia Y, Surani A, Baxi R. Genital lichen sclerosus et atrophicus in females: an update. Indian J Sex Transm Dis AIDS 2019; 40 (1): 6–12. DOI: 10.4103/ijstd.IJSTD_23_19
5. Haefner HK, Welch KC, Rolston AM et al. Genomic profiling of vulvar lichen sclerosus patients shows possible pathogenetic disease mechanisms. J Low Genit Tract Dis 2019; 23 (3): 214–9.
6. Apolikhina I.A., Sokolova A.V. Lechenie skleroziruiushchego likhena vul'vy: ot standartov k innovatsiiam. Akusherstvo i ginekologiia. 2020; 8 (in Russian).
7. Tran DA, Tan X, Macri CJ et al. Lichen sclerosus: an autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int J Biol Sci 2019; 15 (7): 1429–39.
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Авторы
В.В. Логинов*1, А.В. Вартанов1,2, С.А. Фейгин1, А.В. Соколова1, И.А. Аполихина1,3
1 ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*v_loginov@oparina4.ru
1 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia;
3 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*v_loginov@oparina4.ru
1 ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*v_loginov@oparina4.ru
________________________________________________
1 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia;
3 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*v_loginov@oparina4.ru
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