Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Real World Evidence of Bempedoic Acid on Efficacy and Safety in Patients with Uncontrolled LDL-c and at High Risk of CVD

Background and Objective: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality worldwide, with high-risk patients requiring effective management to reduce their risk of cardiovascular events. Bempedoic acid is a novel therapeutic agent recently approved as an add-on therapy to statins in patients with uncontrolled LDL-c. Bempedoic acid inhibits cholesterol synthesis in the liver, which ultimately reduces the risk of cardiovascular events. Therefore, the present study aims to assess the efficacy and safety of bempedoic acid in patients with uncontrolled LDL-c (Previously on moderate or high-intensity statins) with a high risk of CVD in real-world settings. Methods: This is a multicenter, retrospective, observational study on the data of high-risk-CVD patients collected from Bempedoic Acid on Efficacy and Safety in patients (BEST) Registry. The clinical data of 140 patients who were already on statin therapy and were receiving Bempedoic acid at a dose of 180 mg, along with measurements of the level of LDL-c, HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, serum creatinine was taken into consideration. The primary outcome includes a change in LDL-c level, and secondary outcomes involve a change in the level of HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, and serum creatinine at week 12 and 24. Adverse events were reported at both time points. Results: A total of 140 patients were included in the present study with a mean age of 51.8 ± 9.2 years and had primary confirmed diagnosis of dyslipidemia with uncontrolled LDL-c. The mean levels of LDL-c decreased from the mean baseline value of 142.67 ± 46.49 mg/dL, to 106.78 ±33.92 mg/d; a statistically significant reduction by 23.23% (p < 0.01) at week 12. Similarly, at week 24, the mean LDL-c value reduced to 90.39 ± 38.89 mg/dL. A 33.38 % decrease was observed (p < 0.01). Other parameters such as non-HDL, FPG, PPPG, AST and serum creatinine also showed statistically significant reduction at week 12 and week 24. Conclusion: The present study demonstrates that bempedoic acid is an effective add-on medication in lowering LDL-c levels in high-risk CVD patients with uncontrolled LDL-c.

A study on lipid profile in thyroid dysfunction

Background: Thyroid diseases are among the most common endocrine disorders worldwide. Thyroid hormones play a key role in regulating the synthesis, metabolism, and mobilization of lipids. Levels of circulating lipids may alter in thyroid dysfunction. Aim and Objectives: The aim of the study was to find out the alterations of lipid levels in thyroid dysfunction. Materials and Methods: The study was designed as cross-sectional observational study and analysis of values was done by significant tests difference in means. 20 patients with hypothyroidism, 20 patients with hyperthyroidism, and 20 normal were participated in the study. Levels of total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), LDL-C, and LDL/HDL ratio were estimated and compared. Results: In patients with hypothyroidism, there was an increase in total cholesterol, LDL-C, and triglyceride levels and decrease in HDL-C levels. In hyperthyroidism, total cholesterol, triglycerides, LDL-C, VLDL-C, and LDL/HDL ratio were found to be significantly decreased. Conclusion: Altered thyroid function can lead to significant changes in the lipid profile. Hypothyroidism is an important risk factor for heart diseases. Hence, routine screening of thyroid hormones may be of considerable help for early intervention and treatment of thyroid dysfunction-related cardiac disease.

Comparative study on efficacy and safety of atorvastatin in combination with ezetimibe and atorvastatin monotherapy among patients with dyslipidemia – A randomized and double-blind study

Background: Dyslipidemia is defined as the high-density lipoprotein and apolipoprotein A (apo A) levels <10th percentile and/or total cholesterol, triglycerides, low-density lipoprotein (LDL), apolipoprotein B, or Lipoprotein (a) levels more than the 90th percentile. Aim and Objectives: This study aimed to compare the efficacy and safety of the fixed-dose combination of Atorvastatin and Ezetimibe with Atorvastatin monotherapy among patients with dyslipidemia. Materials and Methods: The present study was a randomized, double-blinded, prospective, and parallel-group study. Ninety-two outpatients of age in between 18 and 70 years from the Department of General Medicine who attended the hospital for the treatment of dyslipidemia were selected as study participants. Among 92 patients, 12 patients did not meet the study criteria. The remaining 80 patients were divided into two treatment groups at random and under double-blind conditions (39 in Group A and 41 in Group B). Each patient in both groups was followed for a period of 4 weeks after initiation of therapy. Total cholesterol and LDL-cholesterol levels were recorded at day 1, 2 weeks, and 4 weeks of therapy. Results: In this study, by the end of the study period (4 weeks), tablet Atorvastatin + tablet Ezetimibe combination therapy showed statistical significance difference in reducing mean total cholesterol and mean serum LDL levels in dyslipidemia cases than the group receiving Atorvastatin monotherapy. Conclusion: Atorvastatin in combination with Ezetimibe was more efficacious than Atorvastatin monotherapy in reducing total blood cholesterol and serum LDL levels. Atorvastatin plus Ezetimibe is equally safer as Atorvastatin monotherapy and well tolerated with fewer adverse effects.

Impact of yoga on lipid parameters in different age groups

Background: Cardiovascular diseases (CVDs) rise first among the causes of death occurring due to non-communicable diseases in the world. The majority of cardiovascular deaths are due to ischemic heart disease and cerebrovascular disease. Among the major risk factors, dyslipidemia is an important risk factor. Hence, the prevention of dyslipidemia results in the prevention of ischemic heart disease. Dyslipidemia can be corrected by drugs but more importantly, it can be prevented by lifestyle modification. Aim and Objectives: Our aim is to observe the impact of yoga on lipid parameters in different age groups. Materials and Methods: We included 54 subjects between the age group of 30 and 60 years for this study. They were categorized into two groups: Group I having ages between 30 and 45 years (n = 23) and Group II having ages between more than 45 years and <60 years (n = 31). The lipid parameters were measured afore of yoga training, at the end of 2 months and after 6 months of yogic practices. Statistical analysis was done using the SPSS version of 20.0. A P value of less than 0.05 is considered as statistically significant. Results: Our study revealed that yoga induces a decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very LDL cholesterol and an increase in high-density lipoprotein cholesterol in both Group I and Group II subjects which were statistically significant. Conclusion: Yoga tends to improve dyslipidemia, a major risk factor for CVDs. A yoga lifestyle can be considered a preventive measure for CVDs.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

OBJECTIVE@#Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population.@*METHODS@#A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.@*RESULTS@#All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.@*CONCLUSION@#In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.

Advances in diagnosis and treatment of familial hypercholesterolemia / 南方医科大学学报

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by abnormal lipoprotein metabolism. Patients with FH have a significantly increased risk of coronary artery disease (CAD) due to long-term exposure to high levels of low-density lipoprotein (LDL). The diagnosis of FH relies heavily on gene detection, and examination of LDL receptor (LDLR) function is of great significance in its treatment. This review summarizes the current advances in the screening, diagnosis, and treatment of FH and functional analysis of LDLR gene mutations.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

Possible Risk Factors for Bone Marrow Fibroplasia in Patients with Polycythemia Vera / 中国实验血液学杂志

OBJECTIVE@#To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients.@*METHODS@#Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression.@*RESULTS@#Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05).@*CONCLUSION@#Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.

Clinical difference analysis and solution of lipid target and goal cut-off point determination of blood lipid management from different detection systems / 中华检验医学杂志

Objective:The results of the three lipid detection systems were compared to analyze their influence on risk stratification and clinical treatment in lipid management, especially the target goal cut-off point determination, and to find ways to reduce the impact on target goal determination of various lipid measurement system.Methods:A total of 196 serum samples with triglyceride TG <4.5 mmol/L were collected from people undergoing physical examinations and in-patients in the Second Xiangya Hospital of Central South University from August to October 2022. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were directly detected with Hitachi-Woke (HW), Roche and Mindray detection systems, respectively. The non high-density lipoprotein cholesterol (non HDL-C) was calculated by formula (TC-HDL-C) and LDL-C (F-LDL-C) was calculated by Friedewald formula, and results from various methodology were compared. The coefficient of variation ( CV) of these six indicators derived from the three detection systems were calculated to evaluate the consistency of the obtained results from different venders. In addition, the Pearson correlation coefficient was analyzed to evaluate the correlation of each indicator among different systems. According to the Chinese Guidelines for Blood Lipid Management, samples were divided into groups with LDL-C levels of <1.4, 1.4-<1.8, 1.8-<2.6, 2.6-<3.4 and ≥3.4 mmol/L according to the recommended LDL-C levels for different risk stratification levels. The sample size and percentage of LDL-C test results from different systems in the same group were counted to evaluate the impact of LDL-C differences between systems on clinical decision-making of blood lipid management. The correction factor was calculated through two methods: (1) The average deviation of LDL-C between systems was estimated by EP9-A3 method; (2) Multiple linear stepwise regression was used to establish the regression model of LDL-C difference and related indexes between systems. The two correction factors were used to correct the deviation of LDL-C value obtained from various systems, and Chi-square test was used to compare the difference of LDL-C grouping consistency rate before and after correction. Result:The average CV values of TG, TC, LDL-C, F-LDL-C, HDL-C, and non HDL-C among the three detection systems were 4.84%, 1.92%, 11.96%, 3.81%, 5.82% and 2.61%, respectively. Correlation analysis showed that when comparing the three systems in pairs, except for LDL-C derived from HW and Roche′s, and Mindray and Roche′s LDL-C ( R 2=0.938 and 0.947), the R 2 of other indicators were all greater than 0.97. The consistency rates of the three systems on LDL-C and F-LDL-C were 51.0% (100/196) and 90.8% (178/196), respectively, according to the risk stratification standard values and the difference was statistically significant ( P<0.05). When comparing in pairs, the consistency rates of Roche and HW, Mindray and HW, Mindray and Roche system LDL-C grouping were 60.7% (119/196), 82.7% (162/196), and 54.1% (106/196), respectively. After adjusting for mean deviation, the group consistency rate of Roche and HW increased to 73.7%-79.4% ( P<0.05), and the group consistency rate of Roche and Mindray increased to 72.3%-79.0% ( P<0.05). After adjusting for difference regression model, the group consistency rate of Roche and HW increased to 82.5%-84.0%, and the group consistency rate of Roche and Mindray increased to 81.0%-89.2%. However, there was no significant change in the group consistency rate of Mindray and HW after adjusting for both correction methods ( P>0.05) .Conclusions:There are significant differences in LDL-C derived from different detection systems, and the consistency rate of grouping according to the lipid-lowering standard value is relatively low, which may affect clinical decision-making in lipid management. Adjusted by the correction factor, the consistency rate of grouping between Roche and HW, Roche and Mindray systems with large differences in LDL-C can be improved. Using the difference multiple linear regression model as a correction factor is superior to the average deviation.

The role and mechanism of MMP13 and LRP1 in abnormal autophagy function of articular chondrocytes in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To investigate the impact of matrix metalloproteinase 13 (MMP13) and low-density lipoprotein receptor-related protein 1 (LRP1) on autophagy of articular chondrocytes in patients with Kashin-Beck disease (KBD).Methods:Human articular cartilage samples obtained from 4 KBD patients and 4 control subjects were collected from Shaanxi Institute for Endemic Disease Prevention and Control, and the expression levels of MMP13 and LRP1 in cartilage tissue were determined using immunohistochemistry (IHC). Chondrocytes were extracted and cultured in vitro, the mRNA and protein expression levels of LRP1 and the autophagy related genes [Beclin 1 (BECN1), microtubule associated protein 1 light chain 3 (LC3)], cartilage injury related genes [MMP13, caspase-3 (CASP3)], chondrocyte differentiation related genes [collagen type Ⅱ alpha 1 chain (COL2A1), and SRY-box transcription factor 9 (SOX9)] were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot (WB), respectively. Chondrocytes from 3 KBD patients were extracted, and MMP13 gene silencing experiment was performed by RNA interference (RNAi) technology, the mRNA and protein expression levels of the above genes were detected by qRT-PCR and WB, respectively. In addition, the antagonist receptor associated protein (RAP) of LRP1 was used to block the LRP1 of human normal chondrocytes (C28/I2 cells), and qRT-PCR and WB were used to detect the mRNA and protein expression levels of LRP1, chondrocyte autophagy, differentiation and cartilage injury related genes, respectively. Results:The IHC results showed that the expression levels of MMP13 (1.67 ± 0.21, 0.59 ± 0.15, 0.51 ± 0.12) in the surface, middle, and deep layers of cartilage tissue of KBD patients were significantly higher than those of control subjects (0.25 ± 0.03, 0.26 ± 0.04, 0.06 ± 0.01), and the differences were statistically significant ( t = - 11.38, P < 0.001; t = - 3.82, - 6.26, P = 0.019, 0.003). The expression levels of LRP1 (0.10 ± 0.02, 0.03 ± 0.01, 0.17 ± 0.03) were significantly lower than those of control subjects (1.63 ± 0.40, 0.44 ± 0.12, 0.34 ± 0.08), and the differences were statistically significant ( t = 6.61, 5.61, 3.64, P = 0.003, 0.005, 0.022). The mRNA and protein expression levels of MMP13, CASP3, SOX9 in chondrocytes of KBD patients were significantly higher than those of control subjects, and the differences were statistically significant ( P < 0.05). The mRNA expression levels of LRP1, LC3, COL2A1 were significantly lower than those of control subjects, and the differences were statistically significant ( P < 0.05). After silencing the MMP13 gene in chondrocytes of KBD patients, there were no significant differences in the mRNA and protein expression levels of LRP1, BECN1, LC3, CASP3, COL2A1, and SOX9 ( P > 0.05). After blocking LRP1 with RAP, the protein expression levels of LRP1, BECN1, LC3, MMP13, COL2A1 and SOX9 in chondrocytes were significantly lower than those in control group ( P < 0.05). Conclusions:There is no direct correlation between MMP13 and abnormal autophagy of articular chondrocytes in KBD patients. After blocking LRP1, the expression of the autophagy related genes BECN1 and LC3 in chondrocytes is decreased.

Prediction of poor prognosis in patients with acute cerebral infarction / 中国医师进修杂志

Objective:To explore the predictive values of serum monocyte chemoattractant protein-1 (MCP-1), high mobility protein B1 (HMGB1), adiponectin (APN) and oxidized low density lipoprotein (ox-LDL) levels on poor prognosis of patients with acute cerebral infarction(ACI).Methods:One hundred and sixty-fivepatients with ACI in Zibo Hospital, Shandong Guoxin Nursing Group from October 2018 to December 2020 were selected as the observation group, and 147 healthy people in the same period were selected as the normal control group. The levels of serum MCP-1, HMGB1, APN and ox-LDL were detected. In addition, the observation group was followed up for 3 months after discharge, and the observation group was divided into good prognosis group and poor prognosis group by modified Rankin Scale score. The levels of serum MCP-1, HMGB1, APN and ox-LDL between the poor prognosis group and the good prognosis group were compared. The influencing factors of poor prognosis in patients with ACI and the predictive value of serum MCP-1, HMGB1, APN and ox-LDL levels on poor prognosis were analyzed by Logistic multiple regression analysis and receiver operating characteristic (ROC) curve.Results:The levels of serum MCP-1, HMGB1 and ox-LDL in the observation group were higher than those in the normal control group: (322.61 ± 65.27) ng/L vs. (163.18 ± 15.12) ng/L, (6.61 ± 3.54) μg/L vs. (2.90 ± 0.41) μg/L, (481.11 ± 177.67) mg/L vs. (247.47 ± 27.13) mg/L; but the level of serum APN was lower than that in the normal control group: (10.63 ± 3.80) μg/L vs. (17.65 ± 2.87) μg/L, there were statistical differences ( P<0.05). After 3 months of follow-up, the incidence rate of poor prognosis in the observation group was 35.15%(58/165). The serum levels of MCP-1, HMGB1 and ox-LDL in the poor prognosis group were higher than those in the good prognosis group: (372.15 ± 71.33) ng/L vs. (295.76 ± 42.23) ng/L, (9.74 ± 3.96) μg/L vs. (4.91 ± 1.62) μg/L, (631.03 ± 196.84) mg/L vs. (399.85 ± 95.07) mg/L; but the serum APN level was lower than that in the good prognosis group: (7.62 ± 2.83) μg/L vs. (12.27 ± 3.22) μg/L, there were statistical differences ( P<0.05). The results of Logistic multiple regression analysis showed that age, hypertension, hyperlipidemia, infarct volume, nerve function defect score, time from onset to treatment and MCP-1, HMGB1, APN and ox-LDL levels were the influencing factors of poor prognosis in patients with ACI ( P<0.05). The results of ROC curve analysis showed that the sensitivity and area under the curve of serum MCP-1, HMGB1, APN and ox-LDL levels in combined predicting the poor prognosis were 98.28% and 0.954, which were higher than the single index evaluation ( P<0.05). Conclusions:The serum levels of MCP-1, HMGB1 and ox-LDL are closely related to the prognosis of ACI patients, and all of them have a certain predictive value for the poor prognosis of patients, but the combined prediction efficiency of four items is more higher.

Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 regulating oxidized low density lipoprotein-induced human brain microvascular endothelial cell damage by targeting microRNA-106b-5p / 解剖学报

Objective To investigate the effect of long non-coding RNA (lncRNA) alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) targeting microRNA (miR) -106b-5p on oxidized low-density lipoprotein (ox-LDL) -induced injury of human brain microvascular endothelial cells. Methods Human brain microvascular endothelial cells (ox-LDL group) were induced by ox-LDL, normal cultured cells were control group (Ctrl); A2M-AS1 overexpression (pcDNAA2M-AS1 group), empty vector (pcDNA group), miR-106b-5p inhibitor (anti-miR-106b-5p group), negative control (anti-miR-NC group), pcDNA-A2M-AS1 with control mimic NC (miR-NC group), pcDNA-A2M-AS1 with miR-106b-5p mimic (miR-106b-5p mimics group) were transfected into cells and treated with ox-LDL, n = 9. Real-time PCR was used to detect the expression levels of A2M-AS1 and miR-106b-5p; Kits were used to detect malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)); Flow cytometry and TUNEL detected apoptosis; Dual luciferase reporter gene assay detected A2M-AS1 and miR-106b-5p targeting; Western blotting detected Bcl-2 and Bax protein expression. Results Compared with the Ctrl group, the expression level of A2M-AS1 in the ox-LDL group decreased, and the activity of SOD and CAT and the protein level of Bcl-2 decreased (P<0.05), while the expression level of miR-106b-5p and the level of MDA increased (P<0.05), and the rate of apoptosis and the protein level of Bax increased (P<0.05). Overexpressing A2M-AS1 or interfering with miR-106b-5p decreased the MDA level, apoptosis rate and Bax protein level after ox-LDL-induced cells, and increased SOD, CAT activity and Bcl-2 protein level (P<0.05). A2M-AS1 targeted miR-106b-5p; upregulation of miR-106b-5p reversed the effect of overexpressed lncRNA A2M-AS1 on ox-LDL-induced injury of human brain microvascular endothelial cells (P < 0.05). Conclusion A2M-AS1 attenuates ox-LDL-induced injury of human brain microvascular endothelial cells by targeting miR-106b-5p.

Mechanism of scutellarein inhibiting foaming of macrophages by promoting cholesterol efflux pathway / 中国药理学通报

Aim To investigate the effects of scutellarein on the macrophage foam cell formation and cholesterol efflux, and the underlying mechanism. Methods THP-1 cells were differentiated with PMA, and the cell viability was detected by MTT assays. The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit. The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking, ELISA, dual-luciferase reporter and Western blot. The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interference. Results Scutellarein dose-dependently inhibited oxLDL-induced cholesterol accumulation, accelerated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1. At the same time, scutellarein could bind PPARγ and initiate its downstream LXRa-ABCAl signaling pathway. In addition, gene silencing of PPARγ not only significantly inhibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux, but also reversed the inhibitory effect of scutellarein on macrophage foaming. Conclusions Scutellarein could promote the cholesterol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway, thereby prevent the macrophage foam cell formation.

Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Research progress on selective tooth agenesis caused by LRP6 gene mutation / 口腔疾病防治

@#Selective tooth agenesis (STA) is an abnormal number of teeth due to genetic factors or the environment and is most commonly observed for permanent teeth. LRP6 is one of the common causative genes of STA and is inherited by an autosomal dominant mechanism, leading to non-syndrome tooth agenesis (NSTA) or syndrome tooth agenesis (STA). NSTA is only involved in tooth number and appearance abnormalities, whereas STA caused by LRP6 gene mutation results abnormal ear development, oral-facial clefting, sparse hair and hypohidrosis. In this paper, we review the phenotype and gene mutation traits of selective STA caused by LRP6 gene mutation identified in recent years and describe 38 patients with tooth agenesis from 24 mutation sites of LRP6 gene. We analyzed the percentage of missing teeth and found that the lateral incisor in the maxilla and the second premolar in the maxilla and mandible were most commonly lost, whereas all central incisors in the maxilla remained. LRP6 gene plays a major role in tooth development via the WNT/β-catenin signaling pathway, and LRP6 gene mutation can lead to a series of abnormal manifestations due to the disruption of the signaling pathway. The literature showed that LRP6 gene mutations occurred mostly at the E1 or E2 subdomain, meaning that STA due to the mutants extracellularly disturbed the WNT/β-catenin signaling pathway. However, mature treatments for selective congenital tooth loss are lacking.

Clinical characteristics and follow-up status of patients aged 75 years and above undergoing coronary stenting and the rate of achieving low-density lipoprotein cholesterol / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical characteristics, long-term follow-up rate, level and control rate of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) aged ≥75 years who underwent percutaneous coronary intervention (PCI) during hospitalization. 【Methods】 We selected ASCVD patients aged ≥75 years with PCI from January 2016 to December 2020 in The First Affiliated Hospital of Xi’an Jiaotong University, collected the baseline data of the patients and the follow-up of 1 month, 3 months, 6 months and 12 months after discharge by HIS system, and analyzed their LDL-C and control rate at each follow-up. 【Results】 A total of 1 129 patients were enrolled in this study, aged 78 (ranging from 75 to 89) years. Among them 72.1% were male; myocardial infarction was the main type of ASCVD (71.5% ); hypertension was the most common risk factor, accounting for 85.2% (717/842), followed by diabetes, 58.6% (493/842); 74.6% met the ultra-high risk criteria of the 2020 Chinese Expert Consensus on Lipid Management in Ultra-High Risk ASCVD Patients, and the LDL-C control rate was only 8.1% . The four routine follow-up rates of 1 129 elderly ASCVD patients were 49.5%, 24.1%, 17.1%, and 24.6%, respectively. The detection rates of LDL-C during follow-up were 26.3%, 5.3%, 10.4%, and 13.8%, respectively. LDL-C control rates in ultra-high risk ASCVD were 59.4%, 45.1%, 37.1%, and 17.6%, respectively, while LDL-C control rates in non-ultra-high risk ASCVD patients were 67.3%, 55.6%, 47.4%, and 44.0%, respectively. 【Conclusion】 The elderly patients with ASCVD-PCI were mainly ultra-high risk patients. The routine follow-up rate and the LDL-C compliance rate during follow-up were low and showed a downward trend.

Familial Hypercholesterolemia / 罕见病研究

Familial hypercholesterolemia (FH) is a group of autosomal co-dominant genetic diseases mainly characterized by abnormal low-density lipoprotein related metabolism. It is one of the most common inherited diseases in children and one of the most serious lipid metabolism diseases which results in various life-threatening cardiovascular diseases and the complications. In recent years, the treatment protocols for FH have diversified thanks to the deeper understanding of the disease in China and abroad and the development of new lipid-lowering drugs. However, the current awareness and diagnosis rate of FH are very low. The treatment of the disease is much inadequate. This paper summarizes the clinical characteristics, diagnosis, screening strategy, and treatment of FH hoping to enhance the understanding and awareness of the disease in the society.

A Case Report of Homozygous Familial Hypercholesterolemia Liver Transplantation / 罕见病研究

Homozygous familial hypercholesterolemia (HoFH) is a rare and serious autosomal genetic metabolic disease. Patients without intervention often die younger than 30 years old from early atherosclerotic cardiovascular disease (ASCVD)incurred by extremely high levels of low-density lipoprotein cholesterol (LDL-C). We present a case of HoFH, a child with compound heterozygous mutation in this study. The effect of conventional lipid-lowering therapy through diet control and lipid-lowering drugs was unsatisfactory. The blood-lipid purification proves effective but has poor compliance and difficult to maintain for a longer time. The patient received orthotopic liver transplantation and had been followed for 2 years, with the patient shows normal LDL-C, well growth and development. We hope the case will provide the clinician with better understanding of the diagnosis and treatment of the rare disease of HoFH.

Association between non-high density lipoprotein-cholesterol fractions and presence of allostatic load among industrial workers

Objectives: Non-high density lipoprotein-cholesterol (non-HDL-C) fraction is the total cholesterol (TC) minus HDL-C. It is not a routinely reported component of lipid profile and is used in lipoprotein lowering therapy and prediction of coronary artery disease, target organ damage and atherosclerosis. Allostatic load (AL) is an imbalance between repetitive chronic exposure to stress and adaptive response. The present study investigates the association between non-HDL-C and its fractions (non-HDL-C/HDL-C, non-HDL-C/TC, non-HDL-C/ triglyceride [TG] and non-HDL-C/low-density lipoprotein-cholesterol [LDL-C]) and the presence of AL to determine, which fractions of non-HDL-C predict the diagnostic accuracy and optimal cut points. Materials and Methods: The study design is cross-sectional and data were collected from 169 male industrial workers. AL was measured using neuroendocrine (cortisol and dehydroepiandrosterone sulphate), cardiovascular (systolic blood pressure, diastolic blood pressure and heart rate), metabolic (TC, TG, HDL-C and LDL-C) and anthropometric (waist-hip ratio and body mass index) factors. The fractions of non-HDL-C/HDL-C, nonHDL-C/TC, non-HDL-C/TG and non-HDL-C/LDL-C were calculated using non-HDL-C, HDL-C, TC, TG and LDL-C values. Results: About 43.2% and 56.8% of workers had low and high AL, respectively. The non-HDL-C and its fractions such as non-HDL-C/HDL-C, non-HDL-C/TC and non-HDL-C/LDL-C were significantly increased in the high AL group. Stepwise regression analysis was used to examine the association between non-HDL-C fractions and AL. The fractions of non-HDL-C (? = 0.785, P = 0.001), non-HDL-C/TC (? = ?0.336, P = 0.001) and nonHDL-C/LDL-C (? = 0.295, P = 0.001) influenced AL by 38.6%. The AUC with 95% CI in the high AL group was as follows: non-HDL-C 0.766 (0.696–0.837, P = 0.001); non-HDL-C/HDL-C 0.638 (0.555–0.721, P = 0.002); nonHDL-C/TC 0.635 (0.552–0.712, P = 0.003) and non-HDL-C/LDL-C 0.520 (0.433–0.607, P = 0.657). Non-HDL-C and its fractions were more precisely predicted in the high AL category of workers than in the low AL category. Non-HDL-C predicted the most precisely, followed by non-HDL-C/HDL-C, non-HDL-C/TC, non-HDL-C/ LDL-C and non-HDL-C/TG. Conclusion: According to the present study, non-HDL-C and its fractions such as non-HDL-C/HDL-C, nonHDL-C/TC and non-HDL-C/LDL-C should be considered regular lipid profiles and could be used as biomarkers to reduce the risk of AL.