Yu V Burmitskaya, O V Vasyukova, P L Okorokov, Z T Zuraeva, O B Bezlepkina
Background: Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as pro-inflammatory adipokines in obesity, and a positive one, increasing in response to physical exertion in the form of myokines.
Aim: To study the features of adipocytokine secretion in children with constitutionally exogenous obesity.
Materials and methods: The study included 80 patients: 60 adolescents aged 15 [13; 16] years with constitutionally exogenous obesity SDS BMI: 3.0 [2.6; 3.3] and 20 control group children aged 16 [15; 17] years without excess weight SDS BMI: -0.3 [-1.25; 0.33]. Commercial enzyme immunoassay kits were used to determine the level of adipomyokines. The compositional composition of the body was evaluated by bioimpedance analysis (InBody 770 analyzer, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoft Inc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05.
Results: Levels of IL-6 and irisin are statistically significantly higher in obese adolescents compared to the control group: 0.55 [0.226; 1.35] pg/ml vs 0.202 [0.128; 0.652] pg/ml (p=0.041) and 11.16 [6.6; 22.76] mcg/ml vs 7.36 [6.48; 9.68] mcg/ml (p=0.043), respectively. Concentrations of IL-6, myostatin and decorin increase with an increase in the degree of obesity: grade I vs III: 0.226 [0.224; 0.398] vs 0.80 [0.36; 1.81] pg/ml (p=0,0197), 25,85 [21,53; 28,23] vs 31.41 [24.36; 35.06] ng/ml (p=0.03), 4065.3 [3244.9; 5245.5] vs 5322.5 [4199.8; 7702.4] pg/ml (p=0.0376), respectively. In obese children, IL-6 levels positively correlate with BMI, SDS BMI and the amount of adipose tissue, and myostatin - with BMI and SDS BMI. The concentration of irisin in the blood serum is significantly higher in obese girls than in obese boys and healthy girls. Obese patients, compared with lean peers, are characterized by a statistically significantly higher content of both fat and lean mass. With the progression of obesity, there is a statistically significant increase in the ratio of fat to lean mass (I degree - 0.66 [0.56; 0.7], III - 0.78 [0.68; 0.98] (p=0.0073).
Conclusion: Patients with obesity and normal body weight have different levels of adipomyokines. An increase in the level of IL-6 with the progression of obesity is directly related to an increase in the content of adipose tissue. Further study of the features of adipocytokine secretion, their relationship with the features of the body composition and metabolic complications in obesity is required.
背景:脂肪酸是由肌肉和脂肪组织的细胞合成并分泌到血液中的。它们既有负代谢作用,在肥胖中起到促炎性脂肪因子的作用,也有正代谢作用,以肌细胞因子的形式增加对体力消耗的反应。目的:研究先天性外源性肥胖儿童脂肪细胞因子分泌的特点。材料和方法:该研究包括80名患者:60名15岁[13;16岁的青少年,具有宪法外源性肥胖SDS BMI:3.0[2.6;3.3]和20名16岁[15;17岁的对照组儿童,没有超重SDS BMI:-0.3[1.25;0.33]。使用商业酶免疫测定试剂盒测定脂肪肌因子水平。早上空腹通过生物阻抗分析(InBody 770分析仪,韩国)评估身体的成分组成。使用STATISTICAv.12.0(StatSoft股份有限公司,美国)进行统计处理。结果以中位数(Me)和四分位数(Q1;Q3)的形式表示,分别对应25和75个百分点。临界显著性水平(p)被假定为<;结果:与对照组相比,肥胖青少年的IL-6和鸢尾素水平在统计学上显著升高:分别为0.55[0.226;1.35]pg/ml vs 0.202[0.128;0.652]pg/ml(p=0.041)和11.16[6.6;22.76]mcg/ml vs 7.36[6.48;9.68]mcg/ml(p=0.043)。IL-6、肌生长抑制素和花色苷的浓度随着肥胖程度的增加而增加:I级与III级:分别为0.226[0.224;0.398]vs 0.80[0.36;1.81]pg/ml(p=0.0197)、25,85[21,53;28,23]vs 31.41[24.36;35.06]ng/ml(p=0.03)、4065.3[3244.9;5245.5]vs 5322.5[419.98;7702.4]pg/ml(p=0.0376)。在肥胖儿童中,IL-6水平与BMI、SDS BMI和脂肪组织量呈正相关,肌生长抑制素与BMI和SDS BMI呈正相关。肥胖女孩血清中鸢尾素的浓度明显高于肥胖男孩和健康女孩。肥胖患者与瘦同龄人相比,其特征是脂肪和瘦物质的含量在统计学上显著较高。随着肥胖的发展,脂肪与瘦的比例在统计学上显著增加(I度-0.66[0.56;0.7],III度-0.78[0.68;0.98](p=0.0073)。结论:肥胖和正常体重患者的脂肪肌因子水平不同。IL-6水平随着肥胖的进展而增加与脂肪组织含量的增加直接相关。需要进一步研究肥胖患者脂肪细胞因子分泌的特征及其与身体成分和代谢并发症特征的关系。
{"title":"[Adipomyokines in children with obesity].","authors":"Yu V Burmitskaya, O V Vasyukova, P L Okorokov, Z T Zuraeva, O B Bezlepkina","doi":"10.14341/probl13250","DOIUrl":"10.14341/probl13250","url":null,"abstract":"<p><strong>Background: </strong>Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as pro-inflammatory adipokines in obesity, and a positive one, increasing in response to physical exertion in the form of myokines.</p><p><strong>Aim: </strong>To study the features of adipocytokine secretion in children with constitutionally exogenous obesity.</p><p><strong>Materials and methods: </strong>The study included 80 patients: 60 adolescents aged 15 [13; 16] years with constitutionally exogenous obesity SDS BMI: 3.0 [2.6; 3.3] and 20 control group children aged 16 [15; 17] years without excess weight SDS BMI: -0.3 [-1.25; 0.33]. Commercial enzyme immunoassay kits were used to determine the level of adipomyokines. The compositional composition of the body was evaluated by bioimpedance analysis (InBody 770 analyzer, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoft Inc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05.</p><p><strong>Results: </strong>Levels of IL-6 and irisin are statistically significantly higher in obese adolescents compared to the control group: 0.55 [0.226; 1.35] pg/ml vs 0.202 [0.128; 0.652] pg/ml (p=0.041) and 11.16 [6.6; 22.76] mcg/ml vs 7.36 [6.48; 9.68] mcg/ml (p=0.043), respectively. Concentrations of IL-6, myostatin and decorin increase with an increase in the degree of obesity: grade I vs III: 0.226 [0.224; 0.398] vs 0.80 [0.36; 1.81] pg/ml (p=0,0197), 25,85 [21,53; 28,23] vs 31.41 [24.36; 35.06] ng/ml (p=0.03), 4065.3 [3244.9; 5245.5] vs 5322.5 [4199.8; 7702.4] pg/ml (p=0.0376), respectively. In obese children, IL-6 levels positively correlate with BMI, SDS BMI and the amount of adipose tissue, and myostatin - with BMI and SDS BMI. The concentration of irisin in the blood serum is significantly higher in obese girls than in obese boys and healthy girls. Obese patients, compared with lean peers, are characterized by a statistically significantly higher content of both fat and lean mass. With the progression of obesity, there is a statistically significant increase in the ratio of fat to lean mass (I degree - 0.66 [0.56; 0.7], III - 0.78 [0.68; 0.98] (p=0.0073).</p><p><strong>Conclusion: </strong>Patients with obesity and normal body weight have different levels of adipomyokines. An increase in the level of IL-6 with the progression of obesity is directly related to an increase in the content of adipose tissue. Further study of the features of adipocytokine secretion, their relationship with the features of the body composition and metabolic complications in obesity is required.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 4","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D V Kurkin, E V Makarova, I S Krysanov, D A Bakulin, A I Robertus, O V Ivanova, Yu A Kolosov, R A Kudrin
Background: Procurement of medicines reflects the demand and frequency of prescribing certain drugs, which makes it possible to assess the quality of medical care and compliance with standards. The Russian pharmaceutical market is dynamically developing and expanding, therefore, the commercial sector of drug circulation is a significant part of it and should be studied along with public procurement. Given the significant number of patients diagnosed with diabetes mellitus (DM) in our country, we considered it appropriate and interesting to analyze the structure and volume of turnover of antidiabetic drugs in the retail trade over five years.
Aim: to assess the dynamics of the cost and sales volumes of hypoglycemic drugs in the commercial sector for 2019-2020 compared to 2016.
Materials and methods: The analysis was made on the basis of the data of antidiabetic drugs purchases in Russian pharmacies in 2016 and 2019-2020, according to 95257 pharmacies data.
Results: In 2020, compared to 2016, we see a significant increase in the number of packages purchases (+14,952,897 rub.) and the purchases total amount (+9,377,975,722 rub.), in parallel with the increase in average price per box of the hypoglycemic drug +199, 57 rub. The average price for DPP4 decreased. The cost per pack of metformin remains one of the lowest, second only to glibenclamide and gliclazide. The most expensive drugs include GLP1 group representatives. Insulin purchases have halved, when budget for GLP1 have increased by 10 times, for SGLT2 by 9.5 times, and for DPP4 by 2.1 times. In 2020, metformin gliclazide, a combination of glibencladimide with metformin, glibenclamide and vildgaliptin remain leaders in the number of purchased packages. The purchase leaders in terms of budget share are: metformin, gliclazide, liraglutide, vildagliptin and dapagliflozinCONCLUSION: There are positive trends in the demand for more effective innovative hypoglycemic drugs, however, the affordability of drugs still dominates over the feasibility of their clinical use, and a high percentage of drug turnover in the commercial sector might indicates insufficient funding for drug provision for patients with diabetes mellitus.
{"title":"[Characteristics of purchases of hypoglycemic agents in pharmacy retail sector in 2016-2020 years dynamics].","authors":"D V Kurkin, E V Makarova, I S Krysanov, D A Bakulin, A I Robertus, O V Ivanova, Yu A Kolosov, R A Kudrin","doi":"10.14341/probl13200","DOIUrl":"10.14341/probl13200","url":null,"abstract":"<p><strong>Background: </strong>Procurement of medicines reflects the demand and frequency of prescribing certain drugs, which makes it possible to assess the quality of medical care and compliance with standards. The Russian pharmaceutical market is dynamically developing and expanding, therefore, the commercial sector of drug circulation is a significant part of it and should be studied along with public procurement. Given the significant number of patients diagnosed with diabetes mellitus (DM) in our country, we considered it appropriate and interesting to analyze the structure and volume of turnover of antidiabetic drugs in the retail trade over five years.</p><p><strong>Aim: </strong>to assess the dynamics of the cost and sales volumes of hypoglycemic drugs in the commercial sector for 2019-2020 compared to 2016.</p><p><strong>Materials and methods: </strong>The analysis was made on the basis of the data of antidiabetic drugs purchases in Russian pharmacies in 2016 and 2019-2020, according to 95257 pharmacies data.</p><p><strong>Results: </strong>In 2020, compared to 2016, we see a significant increase in the number of packages purchases (+14,952,897 rub.) and the purchases total amount (+9,377,975,722 rub.), in parallel with the increase in average price per box of the hypoglycemic drug +199, 57 rub. The average price for DPP4 decreased. The cost per pack of metformin remains one of the lowest, second only to glibenclamide and gliclazide. The most expensive drugs include GLP1 group representatives. Insulin purchases have halved, when budget for GLP1 have increased by 10 times, for SGLT2 by 9.5 times, and for DPP4 by 2.1 times. In 2020, metformin gliclazide, a combination of glibencladimide with metformin, glibenclamide and vildgaliptin remain leaders in the number of purchased packages. The purchase leaders in terms of budget share are: metformin, gliclazide, liraglutide, vildagliptin and dapagliflozinCONCLUSION: There are positive trends in the demand for more effective innovative hypoglycemic drugs, however, the affordability of drugs still dominates over the feasibility of their clinical use, and a high percentage of drug turnover in the commercial sector might indicates insufficient funding for drug provision for patients with diabetes mellitus.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 4","pages":"50-60"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by bilateral benign adrenocortical lesions, which in some cases lead to Cushing syndrome (CS). Due to the low detection, non-specific, erased clinical picture and slow, long-term progression, it is difficult to assess the true prevalence of PBMAH. This also leads to fairly limited literature data. A detailed analysis of biochemical, imaging parameters, the clinical presentations, in particular, an assessment of the course of comorbidities (arterial hypertension (AH), diabetes (DM), osteoporosis), is necessary to develop an algorithm for managing patients with PBMAH.</p><p><strong>Aim: </strong>Analysis of clinical and laboratory characteristics of patients with various forms of PBMAH.</p><p><strong>Materials and methods: </strong>A single-center, retrospective, observational, cross-sectional study was carried out. This study included 110 patients with PBMAH who got referred to the National Research Center for Endocrinology in the period from 2013-2023. We carried out comparative and correlation analysis of hormonal (plasma cortisol concentrations after 1 mg dexamethasone (1-mg DST), urinary free cortisol (СКМ), ACTH), biochemical (glycated hemoglobin), radiological data (nodular tissue volume), course of comorbidities (metabolic syndrome, DM, AH, osteoporosis) in three groups of patients: with overt CS, mild autonomous cortisol excess (MACE) and comorbid diseases, and patients with PBMAH without hormonal activity.</p><p><strong>Results: </strong>Among 110 patients 79.1% were women, median age - 60 [51; 68]. The proportion of hormonally inactive forms of PBMAH was 37.3%, the overt CS and MACE was detected in 25.4 and 37.3% consequently. According to the hormonal -examination data: the cortisol level during 1-mg DST was 173.8 nmol/l [86.0; 441.0], ACTH - 3.35 pg/ml [1.00; 8.00], СКМ - 445.5 [249.0; 900.0]. Statistically significant positive moderate correlations were found between the volume of nodular tissue and the level of cortisol after PDT1 (r=0.40, p<0.001), СКМ (r=0.29, p<0.004), as well as a negative moderate correlation between the volume and the level of ACTH (r=-0.40, p<0.001). When analyzing the prevalence and clinical severity of comorbid conditions, DM was diagnosed in 22 (53.7%), AH in 36 (87.8%), obesity and osteoporosis - 23 (56%) and 3 (7.3%) patients. There was no statistically significant difference in the prevalence of CS-associated diseases among the above groups (p=0.56).</p><p><strong>Conclusion: </strong>PBMAH is a heterogeneous pathology with different clinical, hormonal, and imaging characteristics. A correlation was found between the volume of nodular tissue and the degree of hormonal activity of PBMAH. The obtained results emphasize the difficulty in determining clear indications for surgical treatment in the group of patients with MACE. The radicality of proposed surgical procedure should be weighed agai
{"title":"[Primary bilateral macronodular adrenal hyperplasia: clinical and laboratory features].","authors":"A Chevais, A R Elfimova, D G Beltsevich","doi":"10.14341/probl13301","DOIUrl":"10.14341/probl13301","url":null,"abstract":"<p><strong>Background: </strong>Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by bilateral benign adrenocortical lesions, which in some cases lead to Cushing syndrome (CS). Due to the low detection, non-specific, erased clinical picture and slow, long-term progression, it is difficult to assess the true prevalence of PBMAH. This also leads to fairly limited literature data. A detailed analysis of biochemical, imaging parameters, the clinical presentations, in particular, an assessment of the course of comorbidities (arterial hypertension (AH), diabetes (DM), osteoporosis), is necessary to develop an algorithm for managing patients with PBMAH.</p><p><strong>Aim: </strong>Analysis of clinical and laboratory characteristics of patients with various forms of PBMAH.</p><p><strong>Materials and methods: </strong>A single-center, retrospective, observational, cross-sectional study was carried out. This study included 110 patients with PBMAH who got referred to the National Research Center for Endocrinology in the period from 2013-2023. We carried out comparative and correlation analysis of hormonal (plasma cortisol concentrations after 1 mg dexamethasone (1-mg DST), urinary free cortisol (СКМ), ACTH), biochemical (glycated hemoglobin), radiological data (nodular tissue volume), course of comorbidities (metabolic syndrome, DM, AH, osteoporosis) in three groups of patients: with overt CS, mild autonomous cortisol excess (MACE) and comorbid diseases, and patients with PBMAH without hormonal activity.</p><p><strong>Results: </strong>Among 110 patients 79.1% were women, median age - 60 [51; 68]. The proportion of hormonally inactive forms of PBMAH was 37.3%, the overt CS and MACE was detected in 25.4 and 37.3% consequently. According to the hormonal -examination data: the cortisol level during 1-mg DST was 173.8 nmol/l [86.0; 441.0], ACTH - 3.35 pg/ml [1.00; 8.00], СКМ - 445.5 [249.0; 900.0]. Statistically significant positive moderate correlations were found between the volume of nodular tissue and the level of cortisol after PDT1 (r=0.40, p<0.001), СКМ (r=0.29, p<0.004), as well as a negative moderate correlation between the volume and the level of ACTH (r=-0.40, p<0.001). When analyzing the prevalence and clinical severity of comorbid conditions, DM was diagnosed in 22 (53.7%), AH in 36 (87.8%), obesity and osteoporosis - 23 (56%) and 3 (7.3%) patients. There was no statistically significant difference in the prevalence of CS-associated diseases among the above groups (p=0.56).</p><p><strong>Conclusion: </strong>PBMAH is a heterogeneous pathology with different clinical, hormonal, and imaging characteristics. A correlation was found between the volume of nodular tissue and the degree of hormonal activity of PBMAH. The obtained results emphasize the difficulty in determining clear indications for surgical treatment in the group of patients with MACE. The radicality of proposed surgical procedure should be weighed agai","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"58-67"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O R Shabutdinova, A R Dautov, A A Samkov, A V Kononenko, A F Sargaliev, A R Davletshin, P A Andresova, K R Zarbeeva, D A Torshkhoeva, U A Rakhmonkulov, A A Afanasyev
Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0-29.9 kg/m2 and ≥30.0 kg/m2, respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity - 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: «Semaglutide» and «Obesity». The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity.
超重和肥胖是世界范围内的常见问题,诊断为体重指数(BMI)值分别为25.0-29.9 kg/m2和≥30.0 kg/m2。肥胖患者并发疾病的风险很高,如高血压、2型糖尿病(DM2)、高脂血症、中风甚至某些类型的癌症。2016年俄罗斯联邦超重人口比例为62.0%,肥胖人口比例为26.2%。作者在PubMed信息数据库中进行了电子检索。使用了两个搜索元素:«Semaglutide»和«Obesity»。检索包括从数据库建立之日起至2022年8月发表的研究。研究仅限于临床试验的结果。作者获得了26项结果,但仅考虑了SUSTAIN、PIONEER (Peptide Innovation for Early Diabetes Treatment)和STEP的研究,因为它们是在西马鲁肽被批准用于治疗DM2和肥胖之前进行的原始、随机、对照临床试验。
{"title":"[Semaglutide - effectiveness in weight loss and side effects when used according to studies by SUSTAIN, PIONEER, STEP].","authors":"O R Shabutdinova, A R Dautov, A A Samkov, A V Kononenko, A F Sargaliev, A R Davletshin, P A Andresova, K R Zarbeeva, D A Torshkhoeva, U A Rakhmonkulov, A A Afanasyev","doi":"10.14341/probl13197","DOIUrl":"10.14341/probl13197","url":null,"abstract":"<p><p>Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0-29.9 kg/m2 and ≥30.0 kg/m2, respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity - 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: «Semaglutide» and «Obesity». The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"68-82"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M S Sheremeta, M O Korchagina, R M Guseinova, T E Schmidt, K S Nizhegorodova, N Yu Sviridenko, G A Melnichenko
Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves' disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.
{"title":"[Alemtuzumab-induced Graves' disease].","authors":"M S Sheremeta, M O Korchagina, R M Guseinova, T E Schmidt, K S Nizhegorodova, N Yu Sviridenko, G A Melnichenko","doi":"10.14341/probl13238","DOIUrl":"10.14341/probl13238","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves' disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"51-57"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K I Sharafutdinova, V S Shlyapina, A I Baeva, A A Timurshin, I E Sabanaeva, A G Nakieva, M F Kalashnikova, M N Khabibov
The article discusses various pathophysiological conditions and processes that lead to the development of tumors in diabetes mellitus. These include obesity, hyperglycemia, hyperinsulinemia, inflammation, and oxidative stress. The data of epidemiological studies are given, in which it was found that diabetes mellitus (both type 1 and type 2) increases the risk of developing the female reproductive system tumors, such as ovarian cancer, endometrial cancer, while for cervical cancer, vaginal cancer and vulvar cancer, such a relationship has not been clearly identified.
{"title":"[Diabetes mellitus and the female reproductive system tumors].","authors":"K I Sharafutdinova, V S Shlyapina, A I Baeva, A A Timurshin, I E Sabanaeva, A G Nakieva, M F Kalashnikova, M N Khabibov","doi":"10.14341/probl13282","DOIUrl":"10.14341/probl13282","url":null,"abstract":"<p><p>The article discusses various pathophysiological conditions and processes that lead to the development of tumors in diabetes mellitus. These include obesity, hyperglycemia, hyperinsulinemia, inflammation, and oxidative stress. The data of epidemiological studies are given, in which it was found that diabetes mellitus (both type 1 and type 2) increases the risk of developing the female reproductive system tumors, such as ovarian cancer, endometrial cancer, while for cervical cancer, vaginal cancer and vulvar cancer, such a relationship has not been clearly identified.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"103-110"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E A Pigarova, S Yu Vorotnikova, T B Belotserkovskaya
Given the socio-economic, political and epidemiological changes in the regions of the Russian Federation, the issue of modernizing the training of medical personnel and planning to provide medical organizations with qualified specialists has remained extremely important for several years. The analysis of the survey showed that at present the highly topical issue of staffing the population with endocrinologists and pediatric endocrinologists does not have an unambiguous effective solution. The above measures to reorganize the educational environment require additional revision and correction for the most effective work in the field of medical education. Ultimately, these activities will have an impact on improving the level of training of specialists, improving the personnel situation in the constituent entities of the Russian Federation and improving the quality of medical care for the population of the country.
{"title":"[Educational trajectories of the endocrinological service: the results of a survey].","authors":"E A Pigarova, S Yu Vorotnikova, T B Belotserkovskaya","doi":"10.14341/probl13317","DOIUrl":"10.14341/probl13317","url":null,"abstract":"<p><p>Given the socio-economic, political and epidemiological changes in the regions of the Russian Federation, the issue of modernizing the training of medical personnel and planning to provide medical organizations with qualified specialists has remained extremely important for several years. The analysis of the survey showed that at present the highly topical issue of staffing the population with endocrinologists and pediatric endocrinologists does not have an unambiguous effective solution. The above measures to reorganize the educational environment require additional revision and correction for the most effective work in the field of medical education. Ultimately, these activities will have an impact on improving the level of training of specialists, improving the personnel situation in the constituent entities of the Russian Federation and improving the quality of medical care for the population of the country.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"4-8"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M A Dudina, A A Savchenko, S A Dogadin, A G Borisov, V D Belenyuk
Background: The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves' disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease.
Aim: To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease.
Materials and methods: A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves' disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies.
Results: The study included 36 women with recurrent Graves' disease, middle age 46.34±14.32 years. In patients with Graves' disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves' disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg.
Conclusion: A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.
背景:Graves病不同阶段效应亚群形成的调节性T细胞(regulatory T cells, Treg)含量及其各组分膜上CD25表达水平可决定自身免疫过程的长期持续性,是Graves病免疫治疗的靶点。目的:研究Graves病患者放射性碘治疗(RIT)后动态调节性t血细胞亚群特征及CD25表达水平,以确定Graves病潜在的免疫治疗靶点特异性Treg亚群。材料和方法:本研究采用单中心、前瞻性、队列、开放、对照研究,纳入实验室确诊的Graves病女性患者。采用单克隆抗体直接免疫荧光流式细胞术研究调节性t血细胞亚群特征及CD25表面受体表达水平(MFI)。结果:本组36例女性复发性Graves病患者,中年46.34±14.32岁。与对照组相比,Graves病患者在RIT前和RIT后的整个时间内,初始(CD45R0-CD62L+)和终末分化(CD45R0-CD62L-) Treg的比例较低,RIT后3个月和6个月,具有该表型的细胞数量较RIT前和RIT后1个月显著减少(p<0.001)。在代偿性甲状腺功能减退的背景下,Graves病患者CD25受体的表达变化最显著的是在RIT后3个月和6个月:初分化和终末分化Treg表面的MFI CD25水平降低。结论:发现初生Treg水平下降(显然是由于胸腺的分化过程被破坏)和终末分化Treg水平下降(由于成熟和生存过程),这些细胞表面CD25受体表达降低,并且不依赖于甲状腺功能亢进代偿,TSH受体抗体滴度,先前的噻马唑和RIT保守治疗。获得的新数据揭示了初始和终末分化Treg亚群在免疫发病机制中的作用,并有助于概述进一步开发免疫增强治疗方法的方法。
{"title":"[The features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy].","authors":"M A Dudina, A A Savchenko, S A Dogadin, A G Borisov, V D Belenyuk","doi":"10.14341/probl13223","DOIUrl":"10.14341/probl13223","url":null,"abstract":"<p><strong>Background: </strong>The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves' disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease.</p><p><strong>Aim: </strong>To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease.</p><p><strong>Materials and methods: </strong>A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves' disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies.</p><p><strong>Results: </strong>The study included 36 women with recurrent Graves' disease, middle age 46.34±14.32 years. In patients with Graves' disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves' disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg.</p><p><strong>Conclusion: </strong>A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"35-43"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G S Kolesnikova, N M Malysheva, Z T Zuraeva, L V Nikankina, G A Melnichenko
Background: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed.
Aim: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the "expected prolactin levels" recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain).
Results: For adult men and women reference values were 66-436 and 94-500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the "expected values" of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both -cohorts.
Conclusion: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.
{"title":"[Determination of prolactin reference intervals in different age groups].","authors":"G S Kolesnikova, N M Malysheva, Z T Zuraeva, L V Nikankina, G A Melnichenko","doi":"10.14341/probl13095","DOIUrl":"10.14341/probl13095","url":null,"abstract":"<p><strong>Background: </strong>Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed.</p><p><strong>Aim: </strong>The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the \"expected prolactin levels\" recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain).</p><p><strong>Results: </strong>For adult men and women reference values were 66-436 and 94-500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the \"expected values\" of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both -cohorts.</p><p><strong>Conclusion: </strong>The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"16-23"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R K Mikheev, E N Andreeva, O R Grigoryan, E V Sheremetyeva, Yu S Absatarova, N N Volevodz, E V Loginova
Background: Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable.
Aim: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency.
Materials and methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.110 females (20-75y.o.) have participated in the present research.Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.Group 2: 27 females in physiological menopause without MHTGroup 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.DNA extraction - with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish).Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis.
Results: 1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p<0,006).2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p<0,001).3.Reproductive age females had relatively highest telomere length (p<0,001).4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р<0,001) among females.
Conclusion: Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.
{"title":"[Features of aging replicative and biochemical aspects among females with non-iatrogenic hypergonadotropic hypogonadism].","authors":"R K Mikheev, E N Andreeva, O R Grigoryan, E V Sheremetyeva, Yu S Absatarova, N N Volevodz, E V Loginova","doi":"10.14341/probl13295","DOIUrl":"10.14341/probl13295","url":null,"abstract":"<p><strong>Background: </strong>Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable.</p><p><strong>Aim: </strong>To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency.</p><p><strong>Materials and methods: </strong>Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.110 females (20-75y.o.) have participated in the present research.Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.Group 2: 27 females in physiological menopause without MHTGroup 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.DNA extraction - with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish).Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis.</p><p><strong>Results: </strong>1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p<0,006).2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p<0,001).3.Reproductive age females had relatively highest telomere length (p<0,001).4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р<0,001) among females.</p><p><strong>Conclusion: </strong>Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.</p>","PeriodicalId":20433,"journal":{"name":"Problemy endokrinologii","volume":"69 3","pages":"90-102"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}