Gasto energético en reposo y concentración sérica de lipoproteínas de baja densidad en adultos con hipotiroidismo subclínico leve

La alta prevalencia de hipotiroidismo subclínico en Chile puede deberse a que el límite superior normal de la hormona estimulante del tiroides (TSH) sérica es bajo. Personas con TSH levemente mayor al límite superior pueden ser metabólicamente similares a personas sanas. Se compararon marcadores de acción tiroidea (gasto energético en reposo [GER] y lipoproteína de baja densidad [LDL]) en adultos con hipotiroidismo subclínico leve y con función tiroidea normal con o sin tratamiento con levotiroxina. Se midió GER, perfil lipídico y tiroideo en personas sanas con función tiroidea normal (TSH ≥0,4-<4,5 µUI/ml; n=91); con hipotiroidismo subclínico leve (TSH ≥4,5-≤6,5 µUI/ml; n=5); y con hipotiroidismo clínico tratado con levotiroxina y TSH normal (n=13). Se analizó la LDL en 838 personas sanas con función tiroidea normal y 89 con hipotiroidismo subclínico leve de la Encuesta Nacional de Salud 2016/17 (ENS). El GER, ajustado por peso, sexo y edad, fue similar entre grupos (p=0,71). La LDL fue similar entre personas con función tiroidea normal e hipotiroidismo subclínico leve (91±24 vs. 101±17 mg/dl; p=0,67), y menor en hipotiroidismo tratado (64±22 mg/dl; p<0,01). La LDL no se asoció con TSH pero si inversamente con T4L en mujeres (r=-0,33; p=0,02; n=53). En la ENS, ambos grupos tuvieron similar LDL (p=0,34), la que se asoció inversamente con T4L en mujeres (r=-0,12; p=0,01; n=569) pero no con TSH. Personas sanas con función tiroidea normal y con hipotiroidismo subclínico leve tienen similar GER y LDL. Esto apoya la idea de redefinir el límite superior normal de TSH.

The high prevalence of subclinical hypothyroidism in Chile may be due to the low normal upper limit of serum thyroid-stimulating hormone (TSH). People with TSH slightly higher than the upper limit may be metabolically similar to healthy people. Thyroid action markers (resting energy expenditure [REE] and low-density lipoprotein [LDL]) were compared in adults with mild subclinical hypothyroidism and with normal thyroid function with or without levothyroxine treatment. REE, lipid and thyroid profile were measured in healthy people with normal thyroid function (TSH ≥0,4-<4,5 µUI/ml (n=91); with mild subclinical hypothyroidism (TSH ≥4,5-≤6 µUI/ml; n=5); and with clinical hypothyroidism treated with levothyroxine and normal TSH (n=13). LDL was analyzed in 838 healthy people with normal thyroid function and 89 with mild subclinical hypothyroidism from the 2016/17 National Health Survey (NHS). REE, adjusted for weight, sex and age, was similar between the groups (p=0,71). LDL was similar between people with normal thyroid function and mild subclinical hypothyroidism (91±24 vs. 101±17 mg/dl; p=0,67), and lower in treated hypothyroidism (64±22 mg/dl; p<0,01). LDL was not associated with TSH but was inversely with FT4 in women (r=-0,33; p=0,02; n=53). In the NHS, both groups had similar serum LDL (p=0,34), which was inversely associated with FT4 in women (r=-0,12; p=0,01; n=569), but not with TSH. Healthy people with normal thyroid function and mild subclinical hypothyroidism have similar REE and LDL. These results support the idea of redefining the normal upper limit of TSH.

Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real / Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis

Resumo Fundamento: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. Objetivos: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. Métodos: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. Resultados: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. Conclusões: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Abstract Background: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. Objectives: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. Methods: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Results: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Conclusions: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

Research progress on cholesterol metabolism in the regulation of colorectal cancer / 解放军医学杂志

Cholesterol metabolism is a hot topic in exploration of cancer treatment in recent years,and its complex mechanism of action potentially lays a molecular foundation related to lipid-cancer.However,most studies focus only on cholesterol as a product to understand and analyze the progress of cancer,ignoring the phased effects of related derivatives,regulatory proteins and immune cells in its metabolic process,so whether to find targets to regulate colorectal cancer(CRC)from the cholesterol metabolic pathway has become a research focus.This paper reviews the molecular mechanism and the role of signaling pathways in metabolic reprogramming of CRC starting from the abnormal intracellular cholesterol metabolic pathway in order to provide new ideas for the targeted cholesterol therapy of CRC.

Correlation Between TyG Index,MHR and Coronary Lesions,Myocardial Ischemia in Patients with Coronary Heart Disease,and the Value of Combined Detection / 昆明医科大学学报

Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.

ROBO3 deficiency promotes chemotherapy-induced transition of macrophage to foam cell / 实用医学杂志

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Therapeuti ceffect and potential mechanism of cholesterol sulfate on a mouse model of Hashimoto's thyroiditis / 西安交通大学学报(医学版)

Objective To investigate the therapeutic effect of cholesterol sulfate(CS)on the Hashimoto's thyroiditis mouse model.Methods Female NOD.H-2h4 mice were fed with 0.05％NaI in different periods and treated with CS by intraperitoneal injection for two consecutive weeks.HE staining was used to visualize and score the degree of lymphocyte infiltration in the thyroid;serum levels of thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),thyroxine(T4),and thyroid stimulating hormone(TSH)were detected by ELISA.The proportions of B cells and Treg,Th17,Th1,and Th2 cells were analyzed by immunofluorescence staining flow cytometry.Results HE staining showed that the inflammatory score of thyroid tissue in mice after intraperitoneal injection of CS in the 8-week group and the 16-week group decreased significantly(P＜0.05).In the 64-week group,there was no significant difference between the treatment group and the induction group(P=0.31).Serological analysis showed that after CS intervention,the levels of TgAb and TPOAb in mice induced by 0.05％NaI significantly lowered(P＜0.05)in the 8-week group and the 16-week group,while thyroid function(TSH and T4 levels)of the mice changed significantly only in the 16-week group.Flow cytometry analysis showed that in the 8-week group,after CS intervention the proportions of B lymphocytes and Th1,Th2,Th17 and Treg cells in mice were significantly changed(P＜0.05).Conclusion CS has significant therapeutic and remission effects on the early and middle stages of Hashimoto's thyroiditis.

The causal relationship between blood lipids and muscle atrophy based on Mendelian randomization analysis of two samples / 中国组织工程研究

BACKGROUND:Osteoporosis is often accompanied by sarcopenia and an increased risk of fractures from falls.Recent studies have indicated a close relationship between lipid metabolism and sarcopenia.Abnormal lipid metabolism may directly impact muscle physiological function and metabolism. OBJECTIVE:To investigate the relationship between lipid metabolism and sarcopenia and evaluate their causal relationship using Mendelian randomization. METHODS:Mendelian randomization was used to explore the causal relationship between low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,triglycerides,and muscle mass.Research data from genome-wide association studies were used and a sensitivity analysis was conducted to verify the reliability of the results.Approximate indicators of muscle mass,including trunk lean mass and appendicular lean mass,were used as outcome measures. RESULTS AND CONCLUSION:The study found a negative correlation of low-density lipoprotein cholesterol and triglycerides with muscle mass,while no correlation was observed between high-density lipoprotein cholesterol and muscle mass.The results of the sensitivity analysis indicated a robust causal relationship.Using Mendelian randomization,this study provides evidence of a causal relationship between low-density lipoprotein cholesterol and triglycerides and muscle mass.This finding deepens our understanding of the effects of lipids on sarcopenia and has important clinical implications for the prevention and treatment of sarcopenia and osteoporosis.

Correlation between non-high density lipoprotein cholesterol,homocysteine levels and cognitive impairment,prognosis in patients with thalamic infarction / 新乡医学院学报

Objective To investigate the correlation between non-high density lipoprotein cholesterol(non-HDL-C),homocysteine(Hey)levels and cognitive impairment,prognosis in patients with thalamic infarction.Methods Eighty thalamic infarction patients admitted to Puyang People's Hospital from March 2017 to March 2021 were selected as the research sub-jects.According to Montreal cognitive assessment(MoCA)score,the patients were divided into cognitive impairment group(MoCA score＜26,n=35)and cognitive normal group(MoCA score 26-30,n=45).Another 50 healthy individuals who un-derwent physical examinations during the same period were selected as the control group.The serum cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),Hcy levels of all subjects were detected by fully automated biochemical analyzer,and the non-HDL-C levels were calculated.The correlations between non-HDL-C,Hey levels and MoCA scores were analyzed by Pearson correlation analysis,and the diagnostic efficacy of non-HDL-C,Hcy levels for cognitive impairment of patients with tha-lamic infarction was analyzed by receiver operating characteristic curve.According to the modified Rankin scale(mRS)score,the patients with thalamic infarction were divided into good prognosis group(mRS score ≤2,n=50)and poor prognosis group(mRS score 3-6,n=50).The independent risk factors for poor prognosis of patients with thalamic infarction was analyzed by multivariate logistic regression.Results The serum levels of non-HDL-C and Hcy of patients in the cognitive impairment group were significantly higher than those in the cognitive normal group and control group(P＜0.05);there was no significant difference in the serum non-HDL-C,Hcy levels of subjects between the control group and the cognitive normal group(P＞0.05).The non-HDL-C,Hcy levels were negatively correlated with MoCA scores in thalamic infarction patients(P＜0.05).The area under the curve(AUC)of Hcy level in the diagnosis of cognitive impairment was 0.709,the sensitivity was 0.724 and the specificity was 0.630;the AUC of non-HDL-C level in the diagnosis of cognitive impairment was 0.738,the sensitivity was 0.701 and the specificity was 0.870;the AUC of Hey combined with non-HDL-C in the diagnosis of cognitive impairment was 0.769,the sensitivity was 0.758 and the specificity was 0.889.The diagnostic efficacy of Hey combined with non-HDL-C for cognitive impairment was superior to that of non-HDL-C or Hey alone.Atrial fibrillation,elevated levels of non-HDL-C,Hcy and NIHSS score were independent risk factors for poor prognosis of patients with thalamic infarction(P＜0.05).Conclusion The levels of non-HDL-C and Hey are positively correlated with cognitive impairment in patients with thalamic infarction.The levels of non-HDL-C and Hey can be used to diagnose cognitive impairmnent in patients with thalamic infarction,and the combined detection has a better diagnostic effect.Atrial fibrillation,elevated levels of non-HDL-C,Hcy and NIHSS score are independent risk factors for poor prognosis in patients with thalamic infarction.

CD38 regulates macrophagic cholesterol efflux by promoting lysosome reformation via TFEB / 中国病理生理杂志

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Knockdown of SMARCA4 leads to ferroptosis of HT1080 cells through inhibition of cholesterol synthesis / 中国病理生理杂志

AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P＜0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P＜0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.

Diagnostic value of non-high-density lipoprotein cholesterol, ratio of triglyceride to high-density lipoprotein cholesterol and triglyceride glucose index for metabolic syndrome in adult women / 中华健康管理学杂志

Objective:To investigate the diagnostic value of non-high-density lipoprotein cholesterol (non-HDL-C),ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and triglyceride glucose index (TyG) on metabolic syndrome (MS) in adult women.Methods:This was a cross-sectional study. A total of 24 410 adult women who received health examination in health management center of the Affiliated Hospital of Southwest Medical University were selected from January 2019 to December 2021 as subjects. The subjects′ basic information, physical examination results, and laboratory examination data were collected retrospectively. The relationship between non-HDL-C, TG/HDL-C, TyG, and MS in adult women were examined using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) were calculated to evaluate the diagnostic value of each indicator for MS in adult women.Results:Among 24 410 adult females, 800 (3.3%) were found to have MS. After adjusting for age, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, blood uric acid, history of hypertension, history of diabetes, fatty liver, non HDL-C ( OR=1.608), TG/HDL-C ( OR=1.311), TyG ( OR=13.288) were all risk factors for MS in adult women. non-HDL-C, TG/HDL-C, and TyG, as well as their combined AUC of ROC, were 0.795 (95% CI: 0.742-0.776), 0.909 (95% CI: 0.902-0.917), 0.942 (95% CI: 0.937-0.948), and 0.944 (95% CI: 0.937-0.950), respectively. TyG had the highest diagnostic value for MS in adult women among the three indicators, the optimal cutoff value for TyG was 8.237, with a sensitivity of 93.5% and a specificity of 85.5%. Conclusion:non-HDL-C, TG/HDL-C, TyG, as well as their combination, all demonstrate good diagnostic value for MS in adult women.

Nonlinear relationship between high-density lipoprotein cholesterol and diabetes risk: a secondary analysis based on a Chinese adult cohort study / 中华健康管理学杂志

Objective:To investigate the association between high-density lipoprotein cholesterol (HDL-C) and the risk of diabetes mellitus (DM) in Chinese adults.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study using data from the Chinese health screening program in the DATADRYAD database. Between 2010 and 2016, 211833 Chinese adults aged 20 years or older were screened for diabetes at baseline in 32 sites and 11 cities across the country. Baseline HDL-C level was the target independent variable and the risk of DM at follow-up was the dependent variable. Cox proportional hazards regression analysis assessed the independent association between HDL-C levels and the risk of developing DM. In this paper, the generalized Additive Model (GAM) and the smoothing curve fitting method were used to study the nonlinear relationships. In addition, subgroup analyses were conducted to assess the consistency of the correlations among different subgroup and to further validate the reliability of the results.Results:After adjusting for potential confounding factors such as age, sex and body mass index, HDL-C level was positively correlated with the development of diabetes ( HR=1.43, 95% CI: 1.08-1.90, P=0.012). The level of HDL-C showed a non-linear relationship with the risk of DM, and the inflection point was 1.81 mmol/L. The HR (95% CI) of the left and right sides of the inflection point were 0.94 (0.56-1.55) and 2.54 (1.93-3.30), respectively. When HDL-C>1.81 mmol/L, HDL-C was positively correlated with the occurrence of DM. Each 1.00 mmol/L increase in HDL-C increased the risk of diabetes mellitus by 1.54 times ( P<0.001); when HDL-C<1.81 mmol/L, the risk of diabetes decreased by 6% for every 1.00 mmol/L increase in HDL-C ( P=0.798). Subgroup analysis showed that, in the age, male, BMI 24.5-52.7 kg/m 2 subgroups, all the systolic blood pressure subgroups, diastolic blood pressure 69-77 and 78-164 mmHg (1 mmHg=0.133 kPa) subgroups, total cholesterol 0.02-4.26 and 5.00-17.84 mmol/L subgroups, all the triglyceride subgroups, low-density lipoprotein 0-2.42 and 2.99-12.60 mmol/L subgroups, alanine aminotransferase 23.4-1 508.4 U/L subgroups, aspartate transaminase 0-19.7 and 24.8-1 026.2 U/L subgroups, all the urea nitrogen subgroups, creatinine 61.5-76.9, 77.0-1 116.6 μmol/L subgroups, never smoking subgroup, subgroup with frequent alcohol consumption or family history of diabetes mellitus, the effect values of HDL-C and the risk of diabetes mellitus in Chinese adults showed good stability (all HR>1.00). Conclusions:High levels of HDL-C are associated with an increased risk of DM in Chinese adults. When HDL-C is greater than 1.81 mmol/L, HDL-C is positively correlated with DM.

Correlation of circulating ceramides and residual cholesterol with intracranial atherosclerotic stenosis in elderly stroke patients / 中华老年心脑血管病杂志

Objective To investigate the correlation of ceramides(Cer),triglyceride-glucose(TyG)index,residual cholesterol(RC)and intracranial atherosclerotic stenosis(ICAS)in elderly with ischemic stroke(IS).Methods A total of 209 elderly IS patients admitted in the Affiliated Hospi-tal of Xuzhou Medical University from January to December 2022 were recruited,and according to intracranial artery stenosis,they were divided into stenosis group(n=122)and non-stenosis group(n=87).TyG index and RC levels were calculated after testing different types of Cer.Spearman correlation analysis and logistic regression analysis were used.Results Compared with the non-stenosis group,the stenosis group had significantly larger proportions of higher levels of LP(a),HbA1c,TyG index,RC and Cer16∶0,Cer18∶0,Cer24∶1,Cer16∶0/Cer24∶0,Cer24∶1/24∶0 and Cer18∶0/24∶0,and lower Cer24∶ 0 level(P＜0.05,P＜0.01).The levels of Cer16∶0,Cer18∶0,Cer24∶1,Cer16∶0/24∶0,Cer18∶0/24∶0,Cer24∶1/24∶0,LP(a),HbA1c,TyG index and RC were positively correlated with(r=0.290,0.343,0.383,0.436,0.434,0.481,0.166,0.248,0.140,0.204,P＜0.05,P＜0.01),and Cer24∶0 was negatively with ICAS(r=-0.247,P＜0.01).Cer18∶0,Cer24∶1,Cer16∶0/Cer24∶0,Cer18∶0/Cer24∶0 and RC were important influencing factors for ICAS(P＜0.05,P＜0.01).Conclusion The levels of Cer,TyG index and RC are higher in elderly IS patients,and these indicators might be the risk factors for ICAS.

Efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases / 中华老年心脑血管病杂志

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Diagnostic value of superb microvascular imaging and CTA combined with serum sdLDL-C for hypertension patients with ACI / 中华老年心脑血管病杂志

Objective To investigate the diagnostic value of superb microvascular imaging(SMI)grading,CT angiography(CTA),and serum small and dense low-density lipoprotein cholesterol(sdLDL-C)in elderly hypertension patients with acute cerebral infarction(ACI).Methods A ret-rospective study was conducted on 180 elderly hypertension patients admitted to our hospital from June 2021 to June 2023,and those admitted due to ACI were assigned into ACI group(95 cases)and those without into non-ACI group(85 cases).The SMI grade,CTA,and serum sdLDL-C level were compared between the two groups.ROC curve was plotted to analyze the diagnostic value of SMI grading and CTA combined with serum sdLDL-C for ACI in patients with hyperten-sion.Multivariate logistic regression analysis was employed to analyze the factors affecting the oc-currence of ACI in the patients.Results The ACI group had significantly larger proportion of hy-perlipidemia,and higher DBP,SBP,and HDL-C,and LDL-C than the non-ACI group(P＜0.05).The proportion of SMI grade 2 and grade 3 and serum sdLDL-C level were also greatly higher[35.79％vs 10.59％,43.16％vs 8.24％,(1.62±0.25)mmol/L vs(1.35±0.19)mmol/L,P＜0.01],and the proportion of SMI grade 0 and grade 1 was lower(11.58％vs 51.76％,9.47％vs 29.41％,P＜0.01)in the ACI group than the non-ACI group.ROC curve analysis showed that the AUC value of SMI grade and CTA combined with serum sdLDL-C in diagnosing ACI in patients with hypertension was 0.934(95％CI:0.897-0.972).Multivariate logistic regression analysis in-dicated that SMI grade,CTA,and sdLDL-C were risk factors for ACI in hypertensive patients(P＜0.01).Conclusion Combination of carotid artery plaque SMI grading,CTA,and serum sdLDL-C has high auxiliary diagnostic value for elderly hypertension patients with ACI.

Expression and clinical application of serum cystatin C and high-density lipoprotein cholesterol in AD and VD patients / 中华老年心脑血管病杂志

Objective To investigate the expression of cystatin C(Cys C)and high-density lipopro-tein cholesterol(HDL-C)in the serum of patients with Alzheimer's disease(AD)and vascular dementia(VD),and their clinical application.Methods A total of 40 AD patients(AD group)and 40 VD patients(VD group)admitted to Jinhua Second Hospital from January 2020 to January 2022 were enrolled,and another 40 healthy individuals who taking physical examination in the hospital during the same period were subjected as control group.According to Montreal Cognitive Assessment Scale(MoCA)score,the AD patients were divided into mild(22 cases)and moderate to severe(18 cases)AD groups,and the VD patients were into mild(MoCA score 18-26,24 cases)and moderate to severe(MoCA score＜17,16 cases)VD group.Serum levels of Cys C and HDL-C were detected in all the participants,and the diagnostic efficacy of serum Cys C and HDL-C level for AD and VD was analyzed with ROC curve analysis.Results The serum levels of TC,TG,LDL-C and Cys C were significantly higher,and that of HDL-C was obviously lower in the AD and VD groups than the control group(P＜0.05).The Cys C level in the moderate to severe AD group and the moderate to severe VD group was higher than that in the mild AD group and the mild VD group(P＜0.05).There was no significant difference in HDL-C level among moder-ate to severe AD group,moderate to severe VD group,mild AD group and mild VD group(P＞0.05).The AUC value for the combined Cvs C and HDL-C for diagnosis of AD and VD were 0.980(95％CI:0.943-1.000)and 0.951(95％CI:0.905-0.996),respectively.Conclusion Detec-ting serum Cys C and HDL-C levels is simple and convenient.There are significant differences in their serum levels in the patients with AD and VD when compared with healthy population,which may become reference indicators for screening AD and VD.

Mechanism of Total Saponin of Astragali Radix and Total Alkaloids of Nelumbinis Folium Against Hyperlipidemia Based on PPARγ/LXRα/ABCG1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport （RCT） in hyperlipidemia rats， and to discuss its mechanism. MethodSixty SD rats were randomly divided into control group， high-fat diet group， total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low （17 mg·kg-1+40 mg·kg-1）， middle （34 mg·kg-1+80 mg·kg-1）， high dose （68 mg·kg-1+160 mg·kg-1） groups and simvastatin （2.1 mg·kg-1） group， with 10 mice in each group. The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks. From the 3rd week， except for the control group and the high-fat diet group given distilled water， other groups were given corresponding drugs intragastric treatment for 4 weeks. The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue. The contents of total cholesterol （TC） and total bile acid （TBA） in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer. The mRNA and protein expression levels of peroxisome proliferators-activated receptors γ （PPARγ）， liver X receptors α （LXRα）， ATP-binding cassette transporter G1 （ABCG1） and cholesterol 7α-hydroxylase （CYP7A1） in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the contents or activities of TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， TBA， aspartate aminotransferase （AST）， alanine aminotransferase （ALT） in serum were significantly increased （P<0.01）， and the contents of high-density lipoprotein cholesterol （HDL-C） in the high-fat diet group were significantly decreased （P<0.01）. The hepatocyte was clearly swollen like ballooning degeneration， with a lot of fat vacuoles and red fat droplets. The contents of TC and TBA in liver tissue and feces were significantly increased （P<0.01）， and the mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly decreased （P<0.01）. Compared with the high-fat diet group， the contents or activities of TC， TG， LDL-C， TBA， AST， and ALT in the serum of rats in administered groups were significantly decreased （P<0.01）， while the content of HDL-C was significantly increased （P<0.01）. Hepatocyte swelling was significantly reduced， and the ballooning degeneration， fat vacuoles， and red lipid droplets in liver tissue were significantly decreased. The contents of TC and TBA in liver tissue were significantly decreased （P<0.05， P<0.01）， and the contents of TC and TBA in feces were significantly increased （P<0.05， P<0.01）. The mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly increased （P<0.05， P<0.01）. ConclusionTotal saponin of Astragali Radix-total alkaloids of Nelumbinis Folium has a positive effect on the prevention and treatment of hyperlipidemia rats， and its mechanism may be related to the activation of PPARγ/LXRα/ABCG1 signaling pathway and regulation of RCT.

Correlation Between RC/HDL-C Ratio and Ct-Derived Fractional Flow Reserve in Coronary Heart Disease Patients with Critical Lesions / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of remnant cholesterol （RC）/high-density lipoprotein cholesterol （HDL-C） ratio on coronary computed tomography-derived fractional flow reserve （FFRct） in coronary heart disease （CHD） patients with critical lesions. MethodsA retrospective study was done on patients who were admitted to our department and underwent coronary computed tomography angiography （CCTA） from January 1， 2022 to December 31， 2022. All the 304 culprit vessels from the 219 patients with moderate coronary artery stenosis （50%~70%） were divided into FFRct ischemia group （FFRct≤0.8， N=108） and FFRct non-ischemia group （FFRct>0.8， N=111）. Multivariate logistic regression analysis was used to explore the influencing factors of FFRct≤0.8 in CHD patients with critical lesions. Receiver operating characteristic （ROC） curve was drawn to evaluate the predictive value of RC/HDL-C for FFRct≤0.8. Pearson correlation analysis was used to assess whether there was a correlation between RC/HDL-C and FFRct. ResultsThere were significantly more diabetic patients in FFRct ischemia group （P<0.001）. RC/HDL-C ratio， levels of RC， non-HDL-C， APOB， HbA1c and FPG in FFRct ischemic group were significantly increased （P<0.05）. Pearson correlation analysis showed that the RC/HDL-C ratio， levels of RC， Non-HDL-C， TC， TG， LDL-C， HDL-C， LP（a）， HbA1c， and FPG were all significantly negatively correlated with FFRct values （P<0.05）. Univariate logistic regression analysis showed that diabetes mellitus， RC/HDL-C ratio， levels of RC， non-HDL-C， TG， LP（a）， HbA1c and FPG were significantly correlated with FFRct≤0.8 （P<0.05）. Multivariate logistic regression analysis showed that RC/HDL-C ratio was a predictor of FFRct≤0.80 （OR=4.682， 95%CI 1.197~18.316， P<0.05）. ConclusionsRC/HDL-C ratio is independently correlated with FFRct≤0.8 in CHD patients with moderate stenosis and it is a potential indicator for evaluating coronary functional ischemia.

Association between the risk of increase in total cholesterol and the risk of cholelithiasis： A bidirectional Mendelian randomization study / 临床肝胆病杂志

ObjectiveTo investigate the association between the risk of increase in total cholesterol （TC） and the risk of cholelithiasis by using bidirectional Mendelian randomization （MR）. MethodsThe open gwas public database was used to obtain the single nucleotide polymorphism data associated with TC and cholelithiasis， and a secondary data analysis was performed for all summary data of genome-wide association studies. The genetic loci closely associated with TC or cholelithiasis were selected as exposure or outcome variables， and the bidirectional MR analysis was performed using the methods such as Egger regression， Weighted median， IVW random effects model， and IVW fixed effects model， with odds ratio （OR） values for evaluating the causal relationship between TC and cholelithiasis. ResultsWith TC as the exposure and cholelithiasis as the outcome， TC-cholelithiasis had an overall OR value of 0.91 （95% confidence interval ［CI］： 0.85‍ ‍—‍ ‍0.97） before elimination of heterogeneity and 0.93 （95%CI： 0.89‍ ‍—‍ ‍0.97） after elimination of heterogeneity. With cholelithiasis as the exposure and TC as the outcome， TC-cholelithiasis had an overall OR value of 0.20 （95%CI： 0.06‍ ‍—‍ ‍0.65） before elimination of heterogeneity and 0.28 （95%CI： 0.10‍ ‍—‍ ‍0.83） after elimination of heterogeneity. There was a bidirectional causal relationship between genetically predicted TC and cholelithiasis. ConclusionThis study confirms the bidirectional causal relationship between TC and cholelithiasis. The risk of cholelithiasis decreases with the increase in alleles associated with the elevation of TC level； on the contrary， the risk of elevated TC level decreases with the increase in alleles associated with the onset of cholelithiasis.