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ObjectiveTo investigate the mechanism of Xiaonang Tiaojing decoction(XNTJD)in improving polycystic ovary syndrome with insulin resistance(PCOS-IR)model rats based on anti-Müllerian hormone(AMH)/AMH type Ⅱ receptor(AMHRⅡ)signaling pathway. MethodForty-eight adult female SD rats were randomly divided into the blank group, model group, XNTJD group(11.4 g·kg-1·d-1) and Diane-35 group(0.21 g·kg-1·d-1), PCOS-IR model was established by high-fat and high-sugar diet combined with letrozole in rats of all groups except the blank group, rats in the administration groups were given the corresponding dose of drugs by gavage for 15 days with an interval of 1 d every 4 d, normal saline of the same volume was given to the blank group and the model group. Estrous cycle was recorded daily during treatment. At the end of treatment, body weight and Lee's index were recorded, AMH, luteinizing hormone(LH), LH/follicle stimulating hormone(FSH), testosterone(T)and estradiol(E2)levels were measured by enzyme-linked immunosorbent assay(ELISA), fasting plasma glucose(FPG)was measured by glucometer, fasting insulin(FINS) level was measured by radioimmunoassay(RIA), and the insulin resistance index(HOMA-IR) and insulin sensitivity index(QUICKI)were calculated, triglyceride(TG)and total cholesterol(TC)levels were measured by automatic biochemical analyzer, hematoxylin-eosin(HE)staining was used to observe the morphological changes of the ovary, the levels of AMHRⅡ, bone morphogenetic protein-15(BMP-15)and Smad5 in ovarian tissues were detected by immunohistochemistry(IHC),Western blot was used to analyze the protein expression levels of AMHRⅡ, BMP-15 and Smad5. ResultCompared with the blank group, a large number of leukocytes were observed in the vaginal exfoliated cells of rats in the model group, mainly in diestrus, the levels of body weight, Lee's index, glucose-lipid metabolism indexes(FPG, FINS, HOMA-IR, TG, TC), AMH and sex hormones(LH, LH/FSH, T)were significantly increased(P<0.01), and QUICKI and E2 levels were significantly decreased(P<0.01), there were more cystic bulges on the ovarian surface, more wet weight, more atretic and cystic dilated follicles in the ovarian tissues, and the thickness of granulosa cell layer was reduced without oocytes, the expression level of AMHRⅡ protein in ovarian tissues was significantly increased(P<0.01), and the expression levels of BMP-15 and Smad5 proteins were significantly decreased(P<0.01). Compared with the model group, the exfoliated cells in the vagina of rats treated with XNTJD group showed keratinocytes from the 5th to 6th day of treatment, and a stable estrous cycle gradually appeared, body weight, Lee's index, glucose-lipid metabolism indexes(FPG, FINS, HOMA-IR, TG, TC), AMH and sex hormones(LH, LH/FSH, T)levels were significantly decreased(P<0.05, P<0.01), QUICKI and E2 levels were significantly increased(P<0.01), ovarian surface was smoother and lighter in wet weight, oocytes and mature follicles were observed in ovarian tissues, the thickness of granulosa cell layer increased and the morphology was intact, the expression levels of BMP-15 and Smad5 proteins were significantly increased(P<0.01)and the expression level of AMHRⅡ protein was significantly decreased(P<0.01)in ovarian tissues. ConclusionXNTJD may mediate the up-regulation of BMP-15 and Smad5 in ovarian tissues of PCOS-IR rats by down-regulating AMH/AMHRⅡ, thereby improving ovarian function, sex hormones and glucose-lipid metabolism levels in PCOS-IR rats.
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Objective To explore the characteristics of blood uric acid levels and its correlation with calcium and phosphorus levels, and glucose and lipid metabolism in obese adolescents in weight-loss training camps. Methods In this study, 357 obese adolescents aged 12-18 were selected as the research subjects, and 135 normal-weight adolescents were selected as the controls. The body shape and blood uric acid characteristics of the subjects were measured and analyzed. Further, 59 subjects were selected from the obese adolescents for blood calcium, blood phosphorus and glucose and lipid metabolism index tests to analyze the correlation between blood uric acid level and calcium, phosphorus, and glucose and lipid metabolism indicators. Results The average blood uric acid level of obese adolescents was (527.12±122.94)μmol/L, (566.58±122.51)μmol/L for boys, and (468.35±97.79)μmol/L for girls. The blood uric acid level of the obesity group was significantly higher than that of the control group (P<0.001 for boys, P<0.05 for girls), and it was higher in boys than in girls (P<0.01). Obese adolescents with high uric acid accounted for 73.39%. The HOMA-IR of obese adolescents was 5.79±3.04. The blood uric acid level was significantly correlated with blood calcium, total cholesterol, and low-density lipoprotein cholesterol (P<0.05). Gender and low-density lipoprotein cholesterol were the main influencing factors of blood uric acid (P<0.05). Conclusion Obese adolescents have high blood uric acid levels, low calcium and high phosphorus in the body, and a higher incidence of insulin resistance. There exists a positive correlation between the blood uric acid level and the body's calcium and phosphorus metabolism and glucose and lipid metabolism in obese adolescents. Clinical monitoring of lipid metabolism indicators such as low-density lipoprotein has certain reference value for the prevention and treatment of hyperuricemia.
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There is still a lack of effective strategies for the prevention and treatment of liver cancer, and a deep understanding of its pathogenesis may help to develop new treatment methods. Due to the abnormal changes of lipid metabolism in the development and progression of liver cancer, such process is closely associated with the "phlegm-turbidity" theory in traditional Chinese medicine (TCM). Starting from the changes of lipid metabolism in hepatocellular carcinoma microenvironment, this article discusses the association of the abnormal changes of lipid metabolism in tumor cells and immune cells with the "phlegm-turbidity" theory and the clinical efficacy of phlegm-eliminating therapies in clinical practice. Since the "phlegm-turbidity" theory in TCM plays an important role in the pathogenesis and pathological changes of liver cancer, the analysis of its theoretical connotation helps to clarify pathological mechanism, thereby providing a theoretical basis for the role of TCM in the prevention and treatment of liver cancer.
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AIM: To investigate the expression and correlation of C1q/tumor necrosis factor related protein 9(CTRP9)levels in the serum of patients with different stages of diabetic retinopathy(DR)and diabetic macular edema(DME).METHODS: A total of 135 patients with type 2 diabetes who were admitted to Gansu Provincial Hospital from April 2021 to April 2022 were selected as the experimental group. According to the results of non-mydriatic fundus photography, they were divided into non-DR(NDR)group(n=45), non-proliferative DR(NPDR)group(n=45), proliferative DR(PDR)group(n=45); according to the results of optical coherence tomography, DR patients were divided into DME group(n=51), non-DME group(n=39). In addition, other 45 healthy subjects who matched the age and sex of the experimental group were selected as normal control group. The clinical data and biochemical index test results of subjects in each group were recorded and compared, the correlation between serum CTRP9 level and other biochemical indexes was analyzed, and the risk factors affecting the occurrence of DR and DME were explored.RESULTS: There were significant differences in serum CTRP9 levels among subjects in normal control group, NDR group, NPDR group and PDR group(P<0.001), and normal control group > NDR group > NPDR group > PDR group. There was significant difference in serum CTRP9 level between DME group and non-DME group(P<0.001), and non-DME group > DME group. Spearman rank correlation analysis showed that the level of serum CTRP9 in DR patients was negatively correlated with the course of diabetes(rs=-0.251, P<0.05), the level of serum CTRP9 in DME patients was negatively correlated with fasting blood glucose(FBG)(rs=-0.370, P<0.05)and glycosylated hemoglobin(HbA1c)(rs=-0.421, P<0.05). Logistic multivariate regression analysis showed that the course of diabetes(OR=1.194, 95%CI: 1.068~1.335,P=0.002)and the level of serum CTRP9(OR=0.936, 95%CI: 0.907~0.966,P<0.001)were risk factors for DR. The level of serum CTRP9 was a risk factor affecting the occurrence of DME(OR=0.838, 95%CI: 0.778~0.903, P<0.001).CONCLUSION: The reduction of CTRP9 level is a risk factor for the occurrence of DR and DME, which may be of great significance to the risk assessment of both DR and DME.
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OBJECTIVE To investigate the improvement effects and possible mechanism of Phyllanthus emblica water extracts on lipid metabolism disorder and insulin resistance (IR) in diabetic model rats. METHODS IR model of male SD rats was established and randomly divided into model group, positive control group, P. emblica water extracts high-dose, medium-dose and low-dose groups, and another blank group was set up, with 10 rats in each group. P. emblica water extracts high-dose, medium- dose and low-dose groups were given P. emblica water extract diluent at the doses of 800, 400 and 200 mg/kg respectively; positive control group was given pioglitazone solution 2.7 mg/kg; blank group and model group were given the same volume of normal saline, by intragastrical administration, once a day, for consecutive 4 weeks. The general state of rats was observed, and the body mass and the levels of serum lipid metabolism indexes [triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] were measured; fasting insulin of serum (FINS), insulin resistance index (IRI) and insulin sensitivity index (ISI) were measured and calculated by enzyme-linked immunosorbent assay (ELISA). The pathological morphology of liver tissue was observed by hematoxylin-eosin staining; the expression of glycogen in the liver was observed by periodic acid-Schiff staining, and the staining area was calculated; the protein expressions of peroxisome proliferator-activated receptor γ (PPARγ), nuclear factor κB(NF-κB) and AMP-activated protein kinase (AMPK) were detected by Western blot. RESULTS Compared with blank group, the rats in the model group had obvious symptoms of polydipsia, polyphagia and polyuria, and the serum levels of TC, TG, LDL-C, FINS and IRI were significantly increased (P<0.05), while ISI was significantly reduced (P< 0.05); the structure of hepatic lobule was obviously disordered, the liver cells were deformed and enlarged, and there were many lipid deposits and fat vacuoles; PAS staining area of glycogen was significantly reduced(P<0.05); the protein expression levels of PPARγ and p-AMPK were significantly decreased (P<0.05), while the protein expression level of NF-κB was significantly increased (P<0.05). Compared with model group, the mental state of rats, liver histopathological morphology and glycogen expression were improved significantly in P. emblica water extracts high-dose and medium-dose groups; the levels of the above indicators were significantly reversed(P<0.05). CONCLUSIONS P. emblica water extracts may improve glucose and lipid metabolism disorders, liver function and IR in IR model rats, and regulate IR by activating the PPARγ/AMPK/NF-κB signaling pathway.
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ObjectiveTo explore the effects of Baihu Jia Renshen Tang (BHRS) on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway in the liver of MKR diabetic model mice. MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks,followed by intraperitoneal injection of streptozotocin(STZ)for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose (FBG) of ≥11.1 mmol·L-1. After modeling,the mice were randomly divided into a model group,a BHRS group (12.09 g·kg-1·d-1),and a metformin group (0.065 g·kg-1·d-1),with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration,the mice were sacrificed,followed by the oral glucose tolerance test (OGTT) and FBG detection. Serum very low-density lipoprotein(VLDL)content was determined by semi-quantitative enzyme-linked immunosorbent assay (ELISA). Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin(HE)staining. Western blot was used to detect the protein expression of PI3K,Akt,phosphorylated(p)-PI3K,p-Akt,forkhead box protein O1 (FoxO1),insulin receptor(InsR),and insulin receptor substrate-2(IRS-2) in liver tissues of mice. Real-time polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression of PI3K,Akt,FoxO1,InsR,and IRS-2 in liver tissues of mice. ResultCompared with the control group,the model group showed poor general conditions,abnormal glucose tolerance (P<0.05),increased FBG (P<0.01),abnormal blood lipid metabolism,increased serum total cholesterol (TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and VLDL (P<0.05),decreased level of high-density lipoprotein cholesterol(HDL-C)(P<0.05),fatty degeneration and obvious pathological changes of liver cells,reduced protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),increased protein expression of FoxO1(P<0.05),decreased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and increased FoxO1 mRNA expression(P<0.05). Compared with the model group,the BHRS group showed improved general conditions and glucose and lipid metabolism (P<0.05),improved pathological state of liver cells,increased protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),decreased protein expression of FoxO1(P<0.05),increased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and reduced FoxO1 mRNA expression(P<0.05). ConclusionBHRS can effectively reduce blood glucose,regulate blood lipid metabolism,and improve the pathological state of the liver in MKR diabetic mice,and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.
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Nonalcoholic fatty liver disease (NAFLD) has gradually become a prominent cause affecting human liver health, and the development and progression of NAFLD are associated with metabolic dysfunction, with glucose and lipid metabolism disorder as the key link in this process. Takeda G protein-coupled receptor 5 (TGR5) is one of the main receptors of bile acid and is extensively expressed in the body, and glucose and lipid metabolism mediated by TGR5 plays an important role in the human body. This article summarizes the role and mechanism of TGR5 in glucose and lipid metabolism and the research findings of the treatment of NAFLD based on TGR5, in order to provide a reference for basic and clinical research.
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ABSTRACT Introduction In proportion to the development of the economy, the problem of obesity among adolescents is also increasing. This abnormal lipid metabolism index can influence other physical diseases besides harming the social development of youth. Objective Investigate physical training and the regulation of lipid metabolism in adolescents, improving the metabolic index of obese youth. Methods 80 obese adolescents with equal numbers of both genders were randomly assigned into experimental and control groups. The experimental group received daily 80-min sports training (aerobics, walking, badminton, swimming, and other sports with low intensity and long duration) six times a week for one month, without distinction of exercise intensity or frequency for gender. A comparison method was performed between the groups before and after the intervention with indicators including body weight, BMI, fluid ratio, water measurement, waist, hip, skinfold thickness, FBG, CT, Tg, HDL - C, and LDL - C, among others. Results Physical training can effectively improve adolescents' body shape. Blood indices and other indicators except for HDL-C positively correlate with this body shape. Physical training substantially improved lipid metabolism in obese adolescents. Conclusion The exercise regimen of this experiment proved to be simple and manageable, offering adolescents a healthier physical and more confidence in their daily study, life, and social interaction, but also reducing several diseases caused by obesity. Due to the ease of replication, the sample size can be expanded to universal conclusions, making it feasible to popularize. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução Proporcionalmente ao desenvolvimento da economia, aumenta também o problema da obesidade entre os adolescentes. Esse índice anormal no metabolismo lipídico pode influenciar outras doenças físicas além de prejudicar o desenvolvimento social na juventude. Objetivo Investigar o treinamento físico e a regulação do metabolismo lipídico em adolescentes, melhorando o índice metabólico dos jovens obesos. Métodos 80 adolescentes obesos com número igual de ambos os sexos foram distribuídos aleatoriamente em grupos controlados de experimento e controle. O grupo experimental recebeu treinamentos esportivos diários de 80 minutos (aeróbica, caminhada, badminton, natação e outros esportes com baixa intensidade e longa duração), seis vezes por semana durante um mês, sem distinção de intensidade ou frequência dos exercícios para os sexos. Foi realizado o método de comparação entre os grupos, antes e após a intervenção, com indicadores incluindo peso corporal, IMC, taxa de líquidos, medição de água, cintura, quadril, espessura de dobras cutâneas, FBG, CT, Tg, HDL - C, LDL - C entre outros. Resultados O treinamento físico pode melhorar efetivamente a forma corporal dos adolescentes. Índices sanguíneos e outros indicadores com exceção do HDL-C estão positivamente correlacionados com essa forma corporal. O treinamento físico melhorou substancialmente o metabolismo lipídico de adolescentes obesos. Conclusão O esquema de exercícios deste experimento demonstrou-se simples e viável, oferecendo aos adolescentes um físico mais saudável e mais confiança no processo de estudo diário, vida e interação social, mas também reduzir diversas doenças causadas pela obesidade. Devido a facilidade de replicação, o número de amostrar pode ser expandido para conclusões universais, viabilizando a sua popularização. Nível de evidência II; Estudos terapêuticos - investigação dos desfechos do tratamento.
RESUMEN Introducción Proporcionalmente al desarrollo de la economía, el problema de la obesidad entre los adolescentes también aumenta. Este índice anormal en el metabolismo lipídico puede influir en otras enfermedades físicas además de perjudicar el desarrollo social en la juventud. Objetivo Investigar el entrenamiento físico y la regulación del metabolismo lipídico en adolescentes, mejorando el índice metabólico de los jóvenes obesos. Métodos 80 adolescentes obesos con igual número de ambos sexos fueron distribuidos aleatoriamente en los grupos de experimento y de control. El grupo experimental recibió 80 minutos diarios de entrenamiento deportivo (aeróbic, marcha, bádminton, natación y otros deportes de baja intensidad y larga duración), seis veces a la semana durante un mes, sin distinción de intensidad o frecuencia de los ejercicios para los sexos. Se realizó un método de comparación entre los grupos, antes y después de la intervención, con indicadores que incluían el peso corporal, el IMC, la tasa de líquidos, la medición del agua, la cintura, la cadera, el grosor de los pliegues cutáneos, FBG, CT, Tg, HDL - C, LDL - C, entre otros. Resultados El entrenamiento físico puede mejorar eficazmente la forma corporal de los adolescentes. Los índices sanguíneos y otros indicadores, excepto el HDL-C, están positivamente correlacionados con esta forma corporal. El entrenamiento físico mejoró sustancialmente el metabolismo de los lípidos en los adolescentes obesos. Conclusión El esquema de ejercicios de este experimento demostró ser simple y factible, ofreciendo a los adolescentes un físico más saludable y más confianza en el proceso de estudio diario, la vida y la interacción social, pero también reduciendo varias enfermedades causadas por la obesidad. Debido a la facilidad de replicación, el tamaño de la muestra puede ampliarse para obtener conclusiones universales, lo que permite su popularización. Nivel de evidencia II; Estudios terapêuticos - investigación de los resultados del tratamiento.
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SUMMARY OBJECTIVE: The objective of this study, carried out at the university hospital of the Federal University of Rio Grande, was to assess whether the treatment of chronic hepatitis C with direct-acting antivirals and the sustained virological response will affect the metabolic influences of the hepatitis C virus and whether these effects will vary according to genotypes and virus load. METHODS: This is an intervention pre-post study, carried out from March 2018 to December 2019, evaluating 273 hepatitis C virus patients treated with direct-acting antivirals. Inclusion criteria included being monoinfected with hepatitis C virus and achieving sustained virological response . Exclusion criteria included the presence of decompensated cirrhosis or co-infected with hepatitis B virus or human immunodeficiency virus. Genotypes, genotype 1 subtypes, and hepatitis C virus viral load were analyzed. Glucose metabolism was evaluated by the Homeostasis Model Assessment-insulin resistance indices: Homeostasis Model Assessment-β, TyG, and HbA1c, measured at the beginning of treatment and in sustained virological response. Statistical analysis with a T test by paired comparison of the means of the variables in the pretreatment and in the sustained virological response. RESULTS: Homeostasis Model Assessment-insulin resistance analysis: there were no significant differences between pretreatment and sustained virological response. Homeostasis Model Assessment-β analysis: significant increase in genotype 1 patients (p<0.028). TyG index analysis: significant increase in genotype 1b (p<0.017), genotype 3 (p<0.024), and genotype non-1 with low viral load (p<0.039). HbA1c analysis: significant decrease in genotype 3 (p<0.001) and genotype non-1 patients with low viral load (p<0.005). CONCLUSION: We detected significant metabolic influences after sustained virological response: impairment in lipid profile and improvements in the glucose metabolism. We found significant differences in genotype dependence, genotype 1 subtypes, and viral load.
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Abstract Objective: To analyze the lipid profile and cardiovascular risk of overweight and obese adolescents and correlate the findings with anthropometric measurements. Methods: This is a cross-sectional study on overweight and obese adolescents of both sexes (aged 14 to 18 years old). The collected variables were sex, weight, height, age, total cholesterol, triglycerides, High-density lipoprotein (HDL) and low-density lipoprotein (LDL). The Atherogenic Index of Plasma and Castelli Risk Indices I and II were calculated. These indices were classified into cutoff points to stratify cardiovascular risk. The anthropometric profile was evaluated by Z score according to Body Mass Index for age. Significance level was considered as p≤0.05. Results: A total of 146 adolescents participated in the study; the mean age was 16.4±1.1 years and most of them were girls (74.7%) and obese (52.7%). The prevalent dyslipidemias were high triglycerides (47.9%), LDL (26.7%), total cholesterol (37.7%), and low HDL (46.6%). Most adolescents presented increased atherogenic risk according to the Atherogenic Index of Plasma (55.5%); 15.1% presented high cardiovascular risk according to Castelli Risk Index I; and 13.7%, according to Castelli Risk Index II. Boys presented higher values of anthropometric measurements and Castelli Risk Indices I and II in relation to girls — who, conversely, presented higher values of HDL. There was a positive correlation of the Z score with Atherogenic Index of Plasma and a negative correlation with HDL. Conclusions: The adolescents of the study presented high prevalence of cardiovascular and atherogenic risk according to the evaluated indices. In addition, the increased cardiovascular risk was correlated with higher Body Mass Index.
RESUMO Objetivo: Analisar o perfil lipídico e os índices de risco cardiovascular de adolescentes com sobrepeso e obesidade e correlacionar os achados com medidas antropométricas. Métodos: Estudo transversal com adolescentes com sobrepeso ou obesidade de ambos os sexos (14 a 18 anos). Foram coletadas as variáveis: sexo, peso, altura, idade, colesterol total, triglicerídeos, lipoproteína de alta densidade (HDL-c) e lipoproteína de baixa densidade (LDL-c). Calcularam-se o índice aterogênico plasmático e os índices de Castelli I e II. Eles foram classificados em pontos de corte para estratificar o risco cardiovascular. O perfil antropométrico foi avaliado por meio do escore Z com base no índice de massa corporal para a idade. Considerou-se o nível de significância p≤0,05. Resultados: Foram incluídos 146 adolescentes, com média de idade de 16,4±1,1 anos, a maioria do sexo feminino (74,7%) e obesa (52,7%). As dislipidemias prevalentes foram: triglicerídeos (47,9%), LDL-c (26,7%), colesterol total (37,7%) elevado e HDL-c baixo (46,6%). A maioria apresentou risco aterogênico aumentado pelo índice aterôgenico plasmático (55,5%); 15,1% apresentaram alto risco cardiovascular segundo o índice de Castelli I e 13,7%, segundo o índice de Castelli II. Os meninos apresentaram valores superiores de medidas antropométricas e índices de Castelli I e II em relação às meninas, que, por outro lado, apresentaram valores superiores de HDL-c. Houve correlação positiva do escore Z com o índice aterôgenico plasmático e negativa com HDL-c. Conclusões: Os adolescentes do estudo apresentaram alta prevalência de risco cardiovascular e aterogênico conforme os índices avaliados. Além disso, o risco cardiovascular aumentado foi correlacionado com maior índice de massa corporal.
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RESUMEN Con el objetivo de describir el perfil lipídico por trimestres de gestación en gestantes sanas, se realizó un estudio descriptivo, de corte transversal, el cual se condujo con 40 embarazadas entre 20 y 35 años, de un universo de 110, pertenecientes al policlínico "Jimmy Hirzel" de Bayamo, Granma, entre enero del 2017 y marzo del 2019. Se determinaron las concentraciones de colesterol total, triglicéridos, HDL-colesterol, LDL-colesterol y VLDL-colesterol. Se utilizó el análisis de varianza de un factor, y la prueba de Tukey de comparación múltiple de parejas de medias. El colesterol, los triglicéridos, el LDL-colesterol y el VLDL-colesterol variaron de forma significativa con el trimestre de gestación. El colesterol total se incrementó en el segundo y tercer trimestre en comparación con el primero, mientras que los triglicéridos, el LDL-colesterol y el VLDL-colesterol se incrementaron en el tercer trimestre en comparación con el primero. El HDL-colesterol no tuvo una variación significativa durante el embarazo. Se concluye que los valores del colesterol total, los triglicéridos, el LDL-colesterol y el VLDL-colesterol varían en relación con el trimestre de la gestación, aumentan de forma significativa en el tercer trimestre en comparación con el primer trimestre del embarazo, en tanto el HDL-colesterol no varía significativamente durante el embarazo.
ABSTRACT In order to describe the lipid profile by trimesters of pregnancy in healthy pregnant women, a descriptive, cross-sectional study was conducted with 40 pregnant women between 20 and 35 years of age, from a universe of 110, belonging to the "Jimmy Hirzel" Hospital in Bayamo, Granma, between January 2017 and March 2019. The concentrations of total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol were determined. One-factor analysis of variance was used, and the Tukey's multiple comparison test of pairs of means Cholesterol, triglycerides, LDL-cholesterol, and VLDL-cholesterol varied significantly with gestational trimester total cholesterol increased in the second and third trimesters compared with the first, while triglycerides, LDL-cholesterol and VLDL-cholesterol increased in the third trimester compared to the first. HDL-cholesterol did not have a significant variation time during pregnancy. It is concluded that the values of total cholesterol, triglycerides, LDL-cholesterol and VLDL-cholesterol vary in relation to the trimester of pregnancy, they increase significantly in the third trimester compared to the first trimester of pregnancy, while HDL-cholesterol does not vary significantly during pregnancy.
RESUMO Com o objetivo de descrever o perfil lipídico por trimestres de gestação em gestantes saudáveis, foi realizado um estudo descritivo, transversal, com 40 gestantes entre 20 e 35 anos, de um universo de 110, pertencentes ao grupo "Jimmy Hirzel" Hospital em Bayamo, Granma, entre janeiro de 2017 e março de 2019. Foram determinadas as concentrações de colesterol total, triglicerídeos, HDL-colesterol, LDL-colesterol e VLDL-colesterol. Foi utilizada a análise de variância de um fator e o teste de comparação múltipla de Tukey de pares de médias Colesterol, triglicerídeos, LDL-colesterol e VLDL-colesterol variou significativamente com o trimestre gestacional O colesterol total aumentou no segundo e terceiro trimestres em comparação com o primeiro, enquanto os triglicerídeos, LDL-colesterol e VLDL-colesterol aumentaram no terceiro trimestre comparado ao primeiro. O HDL-colesterol não teve variação significativa durante a gravidez. Conclui-se que os valores de colesterol total, triglicerídeos, LDL-colesterol e VLDL-colesterol variam em relação ao trimestre de gestação, aumentam significativamente no terceiro trimestre em relação ao primeiro trimestre de gestação, enquanto o HDL-colesterol não não variam significativamente durante a gravidez.
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Objective:To study the different effects of pre-pregnancy obesity (PO), excessive gestational weight gain (EGWG), pre-pregnancy obesity combined with excessive gestational weight gain (PO+EGWG) of maternal rats on glucose and lipid metabolism in neonatal offspring, and to explore the possible mechanisms.Methods:Animal models of PO, EGWG and PO+EGWG were established by feeding SD rats with high-fat diets at different periods. Thirty-six SD rats were randomly divided into four groups, with nine rats in each group. The control group had a normal diet before and during pregnancy. The PO group had a high-fat diet before pregnancy and a normal diet during pregnancy. The EGWG group had a normal diet before pregnancy and a high-fat diet during pregnancy. And the PO+EGWG group had a high-fat diet before and during pregnancy. The body weight of maternal rats before and during pregnancy and the birth weight of neonatal rats were recorded. Nine male neonatal rats in each group were selected, fasting blood glucose levels were detected by glucometer, fasting insulin levels were detected by enzyme-linked immunosorbent assay kit, hepatic triglyceride and cholesterol levels were detected by glycerol phosphate oxidase-peroxidase method, hepatic lipid deposition were observed by hematoxylin-eosin staining and oil red O staining. The mRNA levels of hepatic key genes in glucose metabolism pathway IR, IRS, AKT and lipid metabolism FASN, SREBP1c, PPARα were detected by reverse transcription-polymerase chain reaction analyses.Results:The pre-pregnancy weight of maternal rats in high-fat diet group before pregnancy (PO group and PO+EGWG group) was significantly higher than those in normal diet group (control group and EGWG group). The percentage of weight gain of maternal rats in high-fat diet group during pregnancy (EGWG group and PO+EGWG group) was significantly higher than those in normal diet group (control group and PO group) ( P<0.05). The birth weight of neonatal rats in PO group, EGWG group and PO+EGWG group were significantly higher than that in control group ( P<0.05), and the birth weight of neonatal rats in PO+EGWG group was the largest. The fasting glucose, insulin level and insulin resistance index of newborn rats in PO, EGWG and PO+EGWG groups were higher than those in the control group, and the mRNA levels of IR, IRS and AKT were lower than those in the control group, but the differences were not statistically significant ( P>0.05). The hepatic triglyceride and cholesterol contents and mRNA levels of FASN and SREBP1c were higher in the EGWG and PO+EGWG groups than those in the control group, and the mRNA level of PPARα was higher in the PO+EGWG group than in the control and PO groups, with statistically significant differences ( P<0.05). Conclusions:Animal models of PO, EGWG and PO+EGWG were successfully constructed by feeding SD rats with high-fat diets before pregnancy, during pregnancy, before and during pregnancy. PO+EGWG had the most significant effects on the birth weight and glucose and lipid metabolism in neonatal offspring. Compared with EGWG, PO had a relatively significant effect on glucose metabolism in neonatal offspring. And compared with PO, EGWG had a relatively significant effect on lipid metabolism in neonatal offspring. The effects of maternal obesity on glucose and lipid metabolism in neonatal offspring were considered to be related to the expression changes of genes in glucose and lipid metabolism.
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In recent years, with the continuous studies on tumor metabonomics, more and more results have shown that changes of metabolism play important roles in the occurrence and development of malignant tumor. Carcinogenic factors can destroy the metabolic balance of human body, induce metabolic reprogramming, and then mediate a variety of biological behaviors to partici-pate in the proliferation and invasion of cancer cells. Lipids provide the body with the necessary energy and essential fatty acids, and a variety of lipid molecules and metabolites are involved in cell signal transduction. Lipid metabolism is an important link in the metabolic system of the body, and the relationship between the occurrence and development of pancreatic cancer and lipid metabo-lism is not clear. The purpose of this paper is to reveal the changes of lipid metabolism in pancreatic cancer, summarize some preclinical studies and clinical trials, and deeply explain the research status of abnormal lipid metabolism associated with pancreatic cancer, so as to provide new ideas for the study of pancreatic cancer pathogenesis and accurate treatment.
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Objective:A rat model of excessive gestational weight gain (EGWG) was constructed to investigate the impact of EGWG on fetal hepatic lipid metabolism and the relevant regulatory mechanism.Methods:Healthy Sprague-Dawley rats were caged together and tested for pregnancy.Rats with the sperm observed under microscope were considered pregnant for 0.5 days.Pregnant rats were divided into the normal diet (ND) group and high-fat diet (HFD) group by the random number table method, with 8 rats in each group.The body weight during pregnancy of the pregnant rats was recorded.Cesarean section was performed at day 21.5 of gestation and the birth weight of the fetal rats was recorded.Hepatic lipid deposition of the pregnant and fetal rats was examined by hematoxylin-eosin (HE) staining and oil red O staining.Triglyceride (TG) and cholesterol (TC) levels in livers and serum of the pregnant and fetal rats were detected by glycerol phosphate oxidase-peroxidase(GPO-PAP) method.The mRNA and protein expression levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats were measured by real-time polyme-rase chain reaction (RT-PCR) and Western blot.Differences between the two groups were compared by independent sample t test. Results:There was no difference in pre-pregnancy body weight between the HFD group and the ND group, but the differences in the weight and the weight gain during pregnancy gradually enlarged between the two groups.At day 21.5 of gestation, the weight of the pregnant rats[(467.75±22.05) g vs.(430.88±18.80) g, t=-3.600, P=0.003], the weight gain of the pregnant rats during pregnancy[(181.50±9.68) g vs.(148.50±10.86) g, t=-6.415, P<0.001] and the birth weight of the fetal rats[(5.51±0.17) g vs.(4.85±0.35) g, t=-4.779, P<0.001] of the HFD group were significantly higher than those of the ND group.Both HE staining and oil red O staining presented increased hepatic lipid deposition in the pregnant and fetal rats of the HFD group.The hepatic and serum TG and TC levels of the pregnant and fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). RT-PCR and Western blot showed that the mRNA and protein levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). Conclusions:An EGWG model can be successfully constructed by a 21-day HFD during pregnancy.EGWG can lead to hepatic lipid deposition in the fetal rats.The mechanism may be related to the expression changes of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats.
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Objective:To analyze the detective value of placental tissue resistin, human lipid carrier protein (LCN) and blood glucose and lipid metabolism in pregnant women with gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) , providing guidance for the early treatment of GDM complicated with preeclampsia.Methods:96 pregnant women with GDM complicated with PE (GDM-PE group) admitted to Yantai Yantaishan Hospital from Jan. 2017 to Jan. 2020 were selected and retrospectively studied. According to the ratio of 2:1, the pure GDM pregnant women (GDM group) and 48 normal pregnant women (the control group) were selected. The placenta tissue resistin and LCN levels were determined by immunohistochemistry. Blood samples were collected to determine the glucose and lipid metabolism. The pregnancy outcomes of each group were compared and the relationship between resistin, LCN, glucose and lipid metabolism and GDM complicated with PE was analyzed.Results:Fasting blood-glucose (FBG) was (4.57±0.66) mmol/L in GDM group and (5.23±0.61) mmol/L in GMD-PE group. FINS (11.97±1.5) mIU/L, (15.12±3.52) mIU/L were higher than those of control group (4.11±0.23) mmol/L, (6.75±1.34) mIU/L ( P<0.05) . FBG, FINS, glycosylated hemoglobin (HbA1c) in GDM-PE group were higher than those in GDM group. TC) (6.71±1.63) mmol/L, triglyceride, TG (6.59±0.87) mmol/L was higher than that of control group (5.87±0.73) mmol/L, (4.57±0.59) mmol/L and GDM group (6.02±1.55) mmol/L, (4.71±0.63) mmol/L ( P<0.05) . high density lipoprotein cholesterol (HDL-C) (1.21±0.34) was lower than that of control group (1.54±0.39) and GDM group (1.55±0.43) ( P<0.05) . The positive rates of resistin 85.42%, 60.42%, LCN 81.25%, 56.25% in GDM-PE group and GDM group were higher than those in control group 39.58%, 31.25% ( χ2=32.096, 4.167; 34.975, 6.095, both P<0.05) . The positive rates of resistin and LCN in GDM-PE group were higher than those in GDM group ( χ2=11.322, 11.257, both P<0.01) . The gestational age of delivery in GDM-PE group was (37.11±2.06) weeks earlier than that in GDM group (38.21±1.75) weeks and control group (38.36±1.42) weeks ( F=9.836, P<0.05) . The birth weight of neonates (2 905.45±356.79) g was lower than that of control group (3 321.52±366.46) g and GDM group (3 425.14±269.87) g ( F=46.606, P<0.05) . Postpartum blood loss (415.34±126.75) ml was significantly higher than that of GDM group (338.65±105.63) ml and control group (298.42±75.26) ml ( F=19.932, P<0.05) . The preterm birth rate of 20.83% was higher than that of the GDM group (8.33%) and the control group (4.17%) ( χ2=9.075, P<0.05) . The postpartum blood loss of the GDM group was higher than that of the control group ( t=-2.148, P<0.05) . The incidences of fetal distress, premature rupture of membranes, fetal growth restriction and postpartum hemorrhage in GDM-PE group were higher than those in control group ( χ2=4.571, 6.867, 5.941, 5.123, P<0.05) . The protein expressions of resistin and LCN in placenta of pregnant women with GDM-PE were positively correlated with FBG, FINS, TC and TG ( r=0.517, 0.463, 0.559, 0.521, 0.485, 0.497, 0.557, 0.571, P<0.05) . Was negatively correlated with HDL-C ( r=-0.317, -0.357, P<0.05) . Conclusions:The positive rate of resistin and LCN in the placenta tissue of pregnant women with GDM complicated with PE is higher than that of GDM and normal pregnant women, their disorder of glucose and lipid metabolism is more obvious, and the incidence of adverse maternal and infant outcomes is higher. It is speculated that resistin and LCN may synergistically affect the metabolism of glucose and lipids causing adverse pregnancy outcomes in GDM complicated with PE.
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Spexin is a new cytokine with a short peptide of 14 amino acids encoded by Ch12orf39, which can be identified by bioinformatics technology.The sequence of Spexin is widely expressed in various organs and is conserved during vertebrate evolution.The physiological effects of Spexin are getting increasing attention in recent years.The studies suggest Spexin plays multiple physiological functions, and the main ligands for biological effects are galanin receptor type 2 and galanin receptor type 3.Spexin palys an important biological role in energy metabolism and homeostasis, cardiovascular function and feeding behavior, and even can affect the regulation of pain and depression relief and reproductive function.This review aims to systemically summarize the Spexin and its related biological functions in metabolic diseases and feeding behavior.
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Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg−1·d−1) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg−1·d−1 BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg−1·d−1 BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.
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Objective:To investigate the predictive effect of postoperative blood lipid metabolism and C-reactive protein/albumin ratio (CAR) on anastomotic fistula after radical resection of esophageal cancer.Methods:A retrospective case-control study was conducted on 256 patients with esophageal squamous cell carcinoma (all aged >50 years) who underwent radical esophagectomy in the thoracic surgery of the Second Affiliated Hospital of Zhengzhou University from January 2017 to December 2020. Total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), ratio of C-reactive protein to albumin (CAR) and hemoglobin test index were collected. According to whether there was anastomotic fistula after operation, the patients were divided into anastomotic fistula group and non-anastomotic fistula group. The measurement data of normal distribution were compared by t-test, the measurement data of non-normal distribution were expressed by M( Q 1, Q 3), the comparison between groups was expressed by Mann-Whitney U test, and the counting data were expressed by (case(%)).The comparison between groups was performed by χ 2 test. Logistic regression model was used for multivariate analysis. ROC curve and Kappa value were used to evaluate the predictive value of total cholesterol and CAR in postoperative anastomotic fistula. Results:The preoperative body mass index (BMI) ((18.71±1.90) kg/m 2) in anastomotic fistula group was higher than that in non-anastomotic fistula group ((20.59±2.88) kg/m 2), and the difference was statistically significant ( t=3.48, P=0.001). The postoperative total cholesterol ((5.44±1.09) mmol/L), LDL-C ((3.82±1.15) mmol/L) and CAR(0.64(0.41, 0.95)) in anastomotic fistula group were higher than those in non-anastomotic fistula group ((4.54±0.94) mmol/L, (2.92±0.76) mmol/L, 0.27(0.13,0.45)). There were significant differences between the two groups (the statistical values were t=4.84, t=5.69, Z=5.16, all P<0.001)). The hemoglobin concentration of 103.20 (84.94,110.48) g/L was lower than that of non anastomotic fistula group (107.68 (99.20,125.20) g/L), the difference was statistically significant ( Z=2.82, P=0.005). Lower BMI( OR=0.652,95% CI 0.482-0.882), higher total cholesterol( OR=3.240,95% CI 1.430-7.340), lower hemoglobin ( OR=0.837,95% CI 0.777-0.902) and higher CAR( OR=2.161,95% CI 1.597-2.925) were the risk factors of anastomotic fistula in esophageal squamous cell carcinoma( P values were 0.006, 0.005, <0.001 and <0.001,respectively). ROC curve analysis showed that the areas under the curve of total cholesterol and CAR were 0.742 (95% CI:0.643-0.841, P<0.001) and 0.790 (95% CI:0.690-0.890, P<0.001) respectively. The cutoff values were 4.915 mmol/L and 0.605, the sensitivity were 80.0% and 80.0%, the specificity were 82.3% and 92.5%, respectively, and the Kappa values were 0.418 and 0.625 respectively (all P<0.001). Conclusion:Total cholesterol and CAR after radical resection of esophageal cancer have a certain predictive value for postoperative anastomotic fistula in patients with esophageal squamous cell carcinoma. The predictive result of CAR is better than that of total cholesterol.
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Objective:To explore the pathogenesis of major depressive disorder(MDD) by comparing the serum glucose and lipid metabolism indicators, levels of glucagon-like peptide-1(GLP-1) in plasma and feces, and the content of specific intestinal flora ( Lactobacillus, Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls. Methods:Totally 80 MDD patients hospitalized from January 1, 2020 to March 30, 2021 and 80 healthy volunteers with normal physical examination in the same period were selected. Blood and fecal samples of patients with MDD and healthy controls were collected respectively. The indicators of serum glucose and lipid metabolism were detected by automatic biochemical analyzer, the concentrations of GLP-1 in plasma and feces were detected by ELISA, and the relative contents of Lactobacillus and Bifidobacterium in feces were detected by real-time PCR. The differences between two groups of glucose and lipid metabolism indicators, GLP-1 levels and the relative contents of Lactobacillus and Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis. Results:Compared with the control group, the levels of serum TC, HDL, and LDL in the MDD group decreased ((3.99±0.85)mmol/L , (4.78±0.86)mmol/L; (1.18±0.29)mmol/L, (1.30±0.28)mmol/L; (2.64±0.70)mmol/L, (3.19±0.69)mmol/L; t=5.559, 2.371, 4.695, all P<0.05). The plasma and fecal GLP-1 levels of the MDD group were lower than those of the control group (plasma: (0.81±0.22)pmol/mL, (1.05±0.26)pmol/mL , t=4.509, P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL, t=2.533, P<0.05). Compared with the control group, the relative contents of Lactobacillus(2.56±1.59, 3.51±2.21) and Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased ( t=2.218, 2.082, both P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity ( r=-0.281, -0.221, -0.437, P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG ( r=-0.580, P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease ( r=-0.298, P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecal Lactobacillus and Bifidobacterium ( r=0.685, 0.428, P<0.01). Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal Lactobacillus and Bifidobacterium. Changes in intestinal flora affect GLP-1 levels. GLP-1 can affect glucose and lipid metabolism and depressive symptoms in patients with MDD by binding to specific receptors in intestinal tract and central nervous system.
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Objective:To investigate the efficacy of levetiracetam combined with low-dose topiramate on epilepsy and its effects on bone metabolism and lipid metabolism in children.Methods:A total of 108 children with epilepsy who received treatment in the First People's Hospital of Yongkang from August 2016 to December 2019 were included in this study. They were randomly allocated to study and control groups ( n = 54/group). The study group was treated with levetiracetam combined with low-dose topiramate. The control group was treated with carbamazepine combined with low-dose topiramate. Before treatment and half a year after treatment, serum alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels, blood Ca 2+ and P 3- concentrations, and bone mineral density (BMD) were determined. Clinical efficacy was evaluated in each group. Results:Half a year after treatment, blood Ca 2+ concentration, blood P 3- concentration, and BMD in the study group were (2.41 ± 0.35) mmol/L, (1.57 ± 0.26) mmol/L, and (2.21 ± 0.52) g/cm2, respectively, which were significantly greater than those in the control group [(2.19 ± 0.27) mmol/L, (1.18 ± 0.15) mmol/L, (1.81 ± 0.38) g/cm, tca2+ = 4.20, tbloodP3- = 5.73, tBMD = 6.42, all P < 0.05). ALP level was significantly lower in the study group than in the control group [(129.78 ± 25.63) U/L vs. (181.55 ± 21.94) U/L, t = 15.39, P < 0.05). Half a year after treatment, TC, TG, and LDL-C levels in the study group were (4.38 ± 0.64) mmol/L, (1.71 ± 0.42) mmol/L, and (1.65 ± 0.32) mmol/L, respectively, which were significantly lower than those in the control group [(4.76 ± 0.83) mmol/L, (1.96 ± 0.45) mmol/L, (1.98 ± 0.34) mmol/L, tTC = 3.81, tTG = 4.14, tLDL-C = 5.58, all P < 0.05]. HDL-C level in the study group was significantly higher than that in the control group [(1.96 ± 0.38) mmol/L vs. (1.63 ± 0.27) mmol/L, tHDL-C = 7.39, P < 0.05]. Half a year after medication, clinical efficacy was significantly higher in the study group than that in the control group (94.44% vs. 81.48%, χ2 = 6.29, P < 0.05). Conclusion:Low-dose topiramate combined with levetiracetam is highly effective on epilepsy in children. The combined therapy has less impact on the levels of bone and lipid metabolism indicators and is suitable for clinical application.