Dan-Lou tablets reduce inflammatory response by inhibiting the activation of NLRP3 inflammasome for coronary heart disease.

BACKGROUND: The activation of the NLRP3 inflammasome has recently been revealed as a novel pathological mechanism of coronary heart disease (CHD). The Dan-Lou tablets (DLT) is widely used in the clinical treatment of CHD and prescription characterized by multi-component and multi-target regulation. However, the anti-inflammatory mechanism of DLT in the treatment of CHD remains unclear. PURPOSE: This study aimed to evaluate the effect of DLT in the treatment of CHD on the priming and activation of the NLRP3 inflammasome and to investigate the underlying anti-inflammatory mechanisms. METHODS: First, CHD rats model were established by a high-fat diet combined with left anterior coronary artery ligation (LADCA) followed by DLT intervention. The therapeutic effect of DLT was evaluated according to cardiac function, lipid level, and cardiac histopathology. Next, data-independent acquisition (DIA) proteomics was used to identify the key differential proteins of DLT intervention in CHD rats, and bioinformatics analysis was performed. Finally, the differentially expressed proteins in the NOD-like signaling pathway were verified based on bioinformatics results, and the priming and activation steps of the NLRP3 inflammasome were detected. RESULTS: In this study, a high-fat diet combined with LADCA was utilized to generate a CHD model, and DLT alleviated myocardial ischemia injury by inhibiting lipid deposition and inflammatory response. Proteomic studies observed that the RNF31, TXN2, and GBP2 of the NOD-like receptor signaling pathway were verified as the key targets of DLT in inhibiting myocardial injury in CHD rats. Furthermore, DLT in the treatment of CHD rats may function through the downregulation of P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and may then reduce the release of the IL-1ß and IL-18 inflammatory factors to play an anti-myocardial injury effect. CONCLUSION: Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD. This study innovatively proposed that DLT further exerts an anti-myocardial injury effect by inhibiting P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and then downregulates the release of the IL-1ß and IL-18 inflammatory factors.

Impaired sensitivity to thyroid hormones is associated with different grades of hypertension: A multicenter cross-sectional study.

BACKGROUND AND AIM: Accumulating evidence suggests a potential link between thyroid function with hypertension. However, the research results are limited, and there is no research to explore the relationship between central and peripheral thyroid hormones (THs) sensitivity and different grades of hypertension in patients with coronary heart disease (CHD). This study aims to prove the complex interaction between thyroid system and blood pressure, and provides new ideas for the assessment of hypertension in patients with CHD. METHODS AND RESULTS: Calculate parameters representing central and peripheral sensitivity to THs. Logistic regression analysis was used to analyze the relationship between central and peripheral THs sensitivity of CHD patients and different grades of hypertension, especially in different ages, sexes, blood glucose levels, smoking, and drinking statuses. Among the 34,310 participants, 19,610 (57.16 %) were diagnosed with hypertension. The risk of hypertension and TSHI (OR: 0.88; 95 % CI: 0.87-0.90; P < 0.001), TT4RI (OR: 0.998; 95 % CI: 0.998-0.999; P < 0.001), TFQI (OR: 0.63; 95 % CI: 0.60-0.67; P < 0.001), PTFQI (OR: 0.63; 95 % CI: 0.59-0.67; P < 0.001) was negatively associated. The risk of hypertension was positively associated with FT3/FT4 (OR: 1.20; 95 % CI: 1.17-1.22; P < 0.001). After stratified analysis, these associations remained significant at different ages, sexes, blood glucose levels, grades of hypertension, smoking, and drinking statuses (P < 0.001). CONCLUSIONS: This study shows that the decrease in central THs sensitivity index and the increase in peripheral THs sensitivity index are associated with a higher risk of hypertension in CHD patients.

Association Between Anemia Status and the Risk of Different Types of Heart Failure: A RCSCD-TCM Study in China.

We investigated the association between anemia status and the risk of heart failure (HF) in patients with coronary heart disease (CHD) based on a multi-center, large-sample and retrospective cross-sectional study including 89,207 patients. Heart failure was categorized as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mid-range ejection fraction (HFmrEF). In multi-adjusted models, compared with patients without anemia, mild anemia (odds ratio [OR] 1.71; 95% confidence interval [CI] 1.53-1.91; P < .001), moderate anemia (OR 3.68; 95% CI, 3.25-4.17; P < .001), and severe anemia (OR 8.02; 95% CI, 6.50-9.88; P < .001) were associated with the risk of HF among CHD patients. Men aged <65 years were more likely to develop HF. In subgroup analyses, the multi-adjusted ORs and 95% CI of HFpEF, HFrEF, and HFmrEF related to anemia were 3.24 (95% CI 1.43-7.33), 2.22 (95% CI 1.28-3.84), and 2.55 (95% CI 2.24-2.89), respectively. These findings suggest that anemia might be associated with increased risk of different types of HF, especially HFpEF.

Relationship Between Serum Uric Acid and Carotid Plaque in Patients With Coronary Artery Disease by Sex and Blood Pressure Status.

The purpose of this study was to explore the sex difference and effects of blood pressure (BP) on the relationship between serum uric acid (SUA) and carotid plaque in patients with coronary heart disease (CHD). This large multicenter retrospective study included 12099 patients with CHD (aged 35-75 years) between January 1, 2014 and September 30, 2020. Patients were divided into three groups according to systolic BP (SBP) and diastolic BP (DBP), and the SUA levels in males and females were converted into three groups. Logistic regression was used to analyze the influence of sex and BP on the relationship between SUA levels and carotid plaque in patients with CHD. In the model of male BP subgroups, using the BP of group A (normal with SBP <120 mmHg and DBP <80 mmHg) as a reference, SUA levels were significantly correlated with the occurrence of carotid plaque under different BP states (P < .001). In contrast, in the model of female BP subgroups, most of these correlations were not statistically significant. Our study showed that SUA levels were significantly associated with carotid plaque occurrence in males with CHD, which remained significant across different BP states.

Fibrinogen/albumin ratio and carotid artery plaques in coronary heart disease patients with different glucose metabolic states: a RCSCD-TCM study.

AIM: The relationship between fibrinogen/albumin ratio (FAR) and carotid artery plaques (CAPs) was investigated in patients with coronary heart disease (CHD). METHODS: A total of 11,624 patients with CHD were enrolled and divided into quartiles based on the FAR (Q1: FAR index ≤ 0.0663; Q2: 0.0664 ≤ FAR index ≤ 0.0790; Q3: 0.0791 ≤ FAR index ≤ 0.0944; Q4: FAR index > 0.0944). Patients were classified into three groups according to their blood glucose levels: normal glucose regulation (NGR), prediabetes mellitus (pre-DM), and diabetes mellitus (DM) groups. Carotid ultrasonography was performed to detect CAPs. The relationship between FAR and CAPs was evaluated using logistic and subgroup analyses. RESULTS: Among 11,624 participants, 8738 (75.14%) had CAPs. Compared with Q1, the odds ratio (OR) of Q4 in patients with CHD was 2.00 (95% confidence interval [CI]: 1.71-2.34) after multivariate adjustment. Taking Q1 as a reference, a higher OR was observed in Q4 of FAR for CAPs in men [OR: 2.26; 95% CI: 1.73-2.95] in the multi-adjusted models. Moreover, multivariate adjustment indicated that the highest OR was observed in patients with CHD and DM (OR: 2.36; 95% CI: 1.80-3.10). CONCLUSIONS: A significant association between FAR and CAPs was observed in patients with CHD, regardless of sex or blood glucose levels. Therefore, FAR may be used as an effective indicator to identify patients at a high risk of CAPs among patients with CHD.

Association of thyroid hormone sensitivity index with stroke in patients with coronary artery disease.

BACKGROUND AND AIMS: Thyroid hormones (THs) will affect the occurrence and prognosis of stroke, and the research on THs sensitivity index and stroke in patients with coronary heart disease (CHD) is scarce. The goal of this study is to look into the relationship between central and peripheral THs sensitivity index and stroke in patients with CHD. METHODS: Between January 1, 2014, and September 30, 2020, 30,160 patients with CHD were enrolled in this study. By computing the thyroid feedback quantile index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI), the central sensitivity indexes to THs was assessed, and the ratio of serum free triiodothyronine (FT3) to serum free thyroxine (FT4) was used to assess peripheral THs sensitivity. The relationship between central and peripheral THs sensitivity index and stroke was investigated using logistic regression, especially in different types of stroke, ages, sexes, and blood glucose levels. RESULTS: Stroke risk is positive associated with TSHI, TFQI, and PTFQI. In subgroup analysis, the OR values of these relationships are higher in people younger than 65 years old, male, and diagnosed with diabetes. In addition, stroke risk was negatively associated with FT3/FT4, and the OR values of these relationships were lower in people older than 65 years, female, and diagnosed with prediabetes. CONCLUSIONS: This study demonstrates that the increase in the central THs sensitivity index and the decrease in the peripheral THs sensitivity index are associated with a higher risk of stroke in CHD patients, and provides new ideas for the assessment of stroke in patients with CHD.

Danlou Recipe promotes cholesterol efflux in macrophages RAW264.7 and reverses cholesterol transport in mice with hyperlipidemia induced by P407.

INTRODUCTION: Liver X Receptor (LXR) agonists could attenuate the development of atherosclerosis but bring excess lipid accumulation in the liver. Danlou Recipe was believed to be a benefit for improving the lipid profile. Thus, it is unclear whether Danlou Recipe could attenuate hyperlipidemia without excess lipid accumulated in the liver of mice. This study aimed to clarify if Danlou Recipe could alleviate the progression of hyperlipidemia in mice without extra lipids accumulated in the liver. METHODS: Male murine macrophage RAW264.7 cells and murine peritoneal macrophages were used for the in vitro experiments. Cellular cholesterol efflux was determined using the fluorescent cholesterol labeling method. Those genes involved in lipid metabolism were evaluated by qRT-PCR and western blotting respectively. In vivo, a mouse model of hyperlipidemia induced by P407 was used to figure out the effect of Danlou Recipe on reverse cholesterol transport (RCT) and hyperlipidemia. Ethanol extract of Danlou tablet (EEDL) was prepared by extracting the whole powder of Danlou Prescription from ethanol, and the chemical composition was analyzed by ultra-performance liquid chromatography (UPLC). RESULTS: EEDL inhibits the formation of RAW264.7 macrophage-derived foam cells, and promotes ABCA1/apoA1 conducted cholesterol efflux in RAW264.7 macrophages and mouse peritoneal macrophages. In the P407-induced hyperlipidemia mouse model, oral administration of EEDL can promote RCT in vivo and improve fatty liver induced by a high-fat diet. Consistent with the findings in vitro, EEDL promotes RCT by upregulating the LXR activities. CONCLUSION: Our results demonstrate that EEDL has the potential for targeting RCT/LXR in the treatment of lipid metabolism disorders to be developed as a safe and effective therapy.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

Fibrinogen-to-Albumin Ratio and Glucose Metabolic States in Patients With Coronary Heart Disease.

This study investigated the relationship between fibrinogen-to-albumin ratio (FAR) and glucose metabolic state in patients with coronary heart disease (CHD). A total of 52,062 patients were enrolled in this study. Patients were classified according to FAR tertiles (T1: FAR < 0.0073; T2: 0.0073 ≤ FAR ≤ 0.0886; T3: FAR ≥ 0.0887). Patients were also classified into the normal glucose regulation (NGR) and elevated blood glucose (EBG) groups. The relationship between FAR and EBG was analyzed using logistic regression, and the association was evaluated according to sex and age. Among the participants, 32,471 (62.4%) had EBG, which was positively associated with FAR (odds ratio [OR], 1.19; 95% confidence interval [CI] 1.15-1.23). The OR of the FAR for EBG in males was higher than that in females (1.25; 95% CI 1.18-1.33 vs 1.15; 95% CI 1.10-1.20). Moreover, the OR of FAR for EBG was greater in patients aged 60 or younger (OR: 1.25; 95% CI 1.18-1.33) than in the elderly patients (over 60 years of age) (OR: 1.15; 95% CI 1.10-1.20). The results indicated a significant relationship between FAR and EBG and this association was higher in males and middle-aged patients.

The Association Between Hemoglobin Glycation Index and Carotid Artery Plaque in Patients With Coronary Heart Disease.

This study aimed to examine the association between the hemoglobin glycation index (HGI) and carotid artery plaque (CAP) in patients with coronary heart disease (CHD). We conducted a cross-sectional analysis of 10,778 patients with CHD. The participants were divided into three groups by HGI tertiles (T1 HGI<-0.44, T2 -0.44 ≤ HGI ≤ 0.15, T3 HGI>0.15). The presence of CAP was used to diagnose by carotid ultrasonography. Logistic regression analysis was used to analyze the association between the HGI and CAP. The association between HGI and CAP was also assessed according to sex, age, smoking status, and drinking status. We further assessed the association between HGI and the ultrasound characteristics of CAP. The baseline analysis showed substantial differences in relevant parameters between the three groups of patients with CHD according to the tertiles of the HGI. Multivariate logistic regression analysis showed that HGI was significantly associated with CAP (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.26-1.39). The association between HGI and CAP exists among different sex, age, smoking, and drinking status. Furthermore, there was a significant and positive association between HGI and all four different echogenicities of the CAP.

Associations Between GGT/ALT Ratio and Carotid Plaque in Inpatients With Coronary Artery Disease: A RCSCD-TCM Study.

This study investigated the relationship between gamma-glutamyltransferase/alanine aminotransferase (GGT/ALT) ratio and carotid plaques in patients with coronary artery disease (CAD). This multicenter retrospective study included 8,255 patients with CAD who were divided according to GGT/ALT quartiles: Q1 (GGT/ALT ≤ 1.00), Q2 (1.00 < GGT/ALT ≤ 1.41), Q3 (1.41 < GGT/ALT ≤ 2.05), and Q4 (GGT/ALT > 2.05). Logistic regression was used to analyze the relationship between GGT/ALT, carotid plaques, and carotid plaque echogenicity. GGT/ALT ratio (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.11-1.21; P < .001) was significantly associated with carotid plaque risk. The degree of relevance was higher in men (OR: 1.71; 95% CI: 1.35-2.15; P < .001) than in women (OR: 1.56; 95% CI: 1.28-1.91; P < .001). The ORs value of carotid plaque risk was higher in middle-aged patients (OR: 2.23; 95% CI: 1.78-2.80; P < .001) than in older patients (OR: 1.77; 95% CI: 1.44-2.18; P < .001). The GGT/ALT ratio was significantly associated with different carotid plaque echogenicity, and the highest OR values were for isoechoic plaques (OR: 1.18; 95% CI: 1.12-1.24; P < .001). These findings suggest that the GGT/ALT ratio might be associated with a high risk of developing carotid plaques and different types of plaque echoes and was more significantly associated with isoechoic plaques.

Associations Between Atherosclerosis and Elevated Serum Alkaline Phosphatase in Patients With Coronary Artery Disease in an Inflammatory State.

BACKGROUND AND AIM: Serum alkaline phosphatase (ALP) has been shown to be associated with cardiovascular disease (CVD) risk. Inflammation is the initiator of atherosclerosis, throughout the life of atherosclerosis. This study investigated the relationship between serum ALP and atherosclerosis in patients with coronary artery disease (CAD) in an inflammatory state. METHODS: This was a multicentre retrospective study including 22,989 patients with CAD. Serum alkaline phosphatase was converted into the quartiles. C-reactive protein (CRP) was assayed as a marker of systemic inflammation. The atherosclerosis index (AI) was used to assess the degree of atherosclerosis. Binary logistic regression was used to analyse the relationship between ALP and AI. Stratified analysis was performed according to sex and age. RESULTS: Elevated serum ALP was associated with the risk of atherosclerosis in patients with CAD, and after quartiling ALP, the OR for Q4 was 1.17 (95% CI 1.08-1.26; p<0.001) when using Q1 as reference. The odds ratio (OR) for ALP and risk of atherosclerosis was higher in patients aged ≤60 years (OR 1.33, 95% CI 1.15-1.53; p<0.001) than in patients aged >60 years (OR 1.11, 95% CI 1.01-1.23; p<0.05), and higher in males (OR 1.21, 95% CI 1.09-1.35; p<0.001) than in females (OR 1.16, 95% CI 1.03-1.31; p<0.05). Q4 (ALP >83.00 U/L) was significantly associated with increased risk of atherosclerosis in the inflammatory state (OR 1.48, 95% CI 1.18-1.86; p<0.001), and it remained after stratified analysis according to sex and age. CONCLUSIONS: The risk of atherosclerosis tended to increase with increasing ALP levels and the correlation between ALP and the degree of atherosclerosis was significantly stronger when ALP was >83.00 U/L. This relationship was more pronounced in inflammatory states, and there were sex and age differences. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04026724.

Effect of Dan-Lou tablets on coronary heart disease revealed by microarray analysis integrated with molecular mechanism studies.

Dan-Lou tablets (DLT) effectively treat coronary heart disease (CHD). However, its pharmacological mechanism in CHD treatment requires further investigation. This study aimed to elucidate the underlying pharmacological mechanisms of DLT in the treatment of CHD through clinical trials, microarray research, bioinformatics analysis, and molecular mechanism research. In this study, DLT improved coagulation function, endothelial injury, and levels of lipids, metalloproteases, adhesion molecules, inflammatory mediators, and homocysteine. The results of molecular biology research demonstrated that DLT can increase the gene and protein expressions of meningioma expressed antigen 5 (MGEA5) and mouse doubleminute 2 (MDM2) and inhibited the gene and protein expressions of signal transcription and transcription activator 5 B (STAT5B), tropomyosin-1 (TPM1), and aromatic hydrocarbon receptor nuclear transpose (ARNT). The results indicate that DLT reduced the extent of vascular endothelial damage in CHD rats by reducing the expressions of STAT5B, TPM1, and MDM2; inhibiting the inflammatory reaction; and increasing the expressions of ARNT and MGEA5.

Seismic evidence for global basalt accumulation in the mantle transition zone.

The mantle's compositional structure reflects the thermochemical evolution of Earth. Yet, even the radial average composition of the mantle remains debated. Here, we analyze a global dataset of shear and compressional waves reflecting off the 410- and 660-km discontinuities that is 10 times larger than any previous studies. Our array analysis retrieves globally averaged amplitude-distance trends in SS and PP precursor reflectivity from which we infer relative wavespeed and density contrasts and associated mantle composition. Our results are best matched by a basalt-enriched mantle transition zone, with higher basalt fractions near 660 (~40%) than 410 (~18-31%). These are consistent with mantle-convection/plate-recycling simulations, which predict that basaltic crust accumulates in the mantle transition zone, with basalt fractions peaking near the 660. Basalt segregation in the mantle transition zone also implies that the overall mantle is more silica enriched than the often-assumed pyrolitic mantle reference composition.

Association between the atherogenic index of plasma and carotid artery plaques in patients with coronary heart disease in different glucose metabolism states: an RCSCD-TCM study in Tianjin, China.

BACKGROUND: The atherogenic index of plasma (AIP) is considered a powerful biomarker of dyslipidemia and atherosclerosis (AS). However, limited evidence is available regarding the relationship between the AIP and carotid artery plaques (CAPs) in patients with coronary heart disease (CHD). METHODS: This retrospective study included 9281 patients with CHD who underwent carotid ultrasound. Participants were divided according to the AIP tertiles: T1, AIP < 1.02; T2, 1.02 ≤ AIP < 1.25; and T3, AIP ≥ 1.25. The presence or absence of CAPs was assessed using carotid ultrasound. Logistic regression was used to analyze the relationship between the AIP and CAPs in patients with CHD. The relationship between the AIP and CAPs was assessed according to sex, age, and glucose metabolic status. RESULTS: The baseline characteristics revealed significant differences in related parameters among patients with CHD after stratification into the three groups according to the AIP tertiles. Compared with T1, the odds ratio (OR) of T3 in patients with CHD was 1.53 (95% confidence interval [CI]:1.35-1.74). The association between AIP and CAPs was higher in females (OR: 1.63; 95% CI: 1.38-1.92) than in males (OR: 1.38; 95% CI: 1.12-1.70). The OR for patients aged ≤60 years (OR: 1.40; 95% CI: 1.14-1.71) was lower than that for patients aged >60 years (OR: 1.49; 95% CI: 1.26-1.76). AIP was significantly associated with the risk of CAPs formation in different glucose metabolic states, with diabetes having the highest OR value (OR: 1.31; 95% CI: 1.19-1.43). CONCLUSION: The AIP and CAPs were significantly associated in patients with CHD, and the association was higher in female than in male patients. The association was lower in patients aged ≤60 years than in patients aged >60 years. Under different glucose metabolism statuses, the association between the AIP and the CAPs among patients with CHD was highest in patients with diabetes.

Relationship between red cell distribution width/albumin ratio and carotid plaque in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China.

BACKGROUND: Red cell distribution width/albumin ratio (RAR) is thought to be associated with the prognosis of a variety of diseases, including diabetes and heart failure. To date, no studies have focused on the relationship between RAR and carotid plaque in patients with coronary heart disease (CHD). METHODS: A total of 10,267 patients with CHD were divided according to RAR quartiles (Q1: RAR ≤ 2.960; Q2: 2.960 < RAR ≤ 3.185; Q3: 3.185 < RAR < 3.441; Q4: RAR ≥ 3.441). Logistic regression was used to analyze the relationship between RAR and carotid plaques in CHD patients. The relationship between RAR and carotid plaques in according to sex, age and glucose regulation state groups were also assessed. RESULTS: Among the 10,267 participants, 75.43% had carotid plaques. After adjusting for confounding factors, RAR was found to be associated with carotid plaque formation (OR: 1.23; 95% CI 1.08-1.39). The risk of carotid plaque formation in the Q4 group was 1.24 times higher than that in the Q1 group. After multivariate adjustment, RAR was associated with the risk of carotid plaque in female (OR: 1.29; 95% CI 1.09-1.52). And the relationship between RAR and carotid plaques in patients younger than 60 years old (OR: 1.43; 95% CI 1.16-1.75) was stronger than that in those older than 60 years old (OR: 1.29; 95% CI 1.10-1.51). Under different glucose metabolism states, RAR had the highest correlation with the risk of carotid plaques in diabetes patients (OR: 1.28; 95% CI 1.04-1.58). CONCLUSIONS: RAR was significantly related to carotid plaques in patients with CHD. In addition, the correlation between RAR and the incidence of carotid plaque in patients with CHD was higher in women and middle-aged and elderly patients. In patients with CHD and diabetes, the correlation between RAR and carotid plaque was higher.

Gut microbiota-SCFAs-brain axis associated with the antidepressant activity of berberine in CUMS rats.

BACKGROUND: The anti-depressant effect of berberine (BBR) has been widely reported. However, the underlying mechanism remains unclear. The microbiota-gut-brain (MGB) axis plays a key role in the pathogenesis of depression. Therefore, we aimed to explore the anti-depressant mechanisms of BBR involving the association of the gut microbiota, neurotransmitters, BDNF, and SCFAs in chronic unpredictable mild stress (CUMS)-induced depressive rats. METHODS: The antidepressant effects of BBR were detected by open-field test, 1 % sucrose preference test and body weight test in CUMS-induced depressive rats. 16S rDNA sequencing was performed to identify the change of gut microbiota. The concentrations of fecal SCFAs were analyzed by GC-MS targeted metabolomics. At the same time, neurotransmitters and BDNF expression were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: BBR improved depression-like behaviors in CUMS rats by increasing the expression of serotonin (5-HT), norepinephrine (NE), dopamine (DA), and BDNF in the hippocampus. BBR regulates Firmicutes, Bacteroidetes, and Lachnospiraceae in depressive rats, resulting in the alteration of the synthesis and metabolism of SCFAs, including acetic, propanoic, and isovaleric acids. LIMITATIONS: Direct evidence that BBR improves depressive behaviors via gut microbiota-SCFAs-brain axis is lacking, and only male rats were investigated in the present study. CONCLUSION: The anti-depressant mechanism of BBR is related to the regulation of the MGB axis via modulating the gut microbiota-SCFAs-monoamine neurotransmitters/BDNF.

Association between sensitivity to thyroid hormones and dyslipidemia in patients with coronary heart disease.

BACKGROUND: Thyroid hormones affect lipid metabolism via central and peripheral regulation. However, there have been few studies on the association between thyroid hormone sensitivity and dyslipidemia. We aimed to investigate the association between thyroid hormone sensitivity and dyslipidemia in patients with coronary heart disease (CHD). METHODS: A total of 31,678 patients with CHD were included in this large multicenter retrospective study. Central thyroid hormone sensitivity was evaluated using the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI); peripheral thyroid hormone sensitivity was assessed by the ratio of free triiodothyronine (FT3)/free thyroxine (FT4). Logistic regression analysis was used to analyze the association between thyroid hormone sensitivity and dyslipidemia. RESULTS: Among 31,678 participants, 21,648 (68.34%) had dyslipidemia. In the multi-adjusted models, the risk of dyslipidemia was positively correlated with TFQI (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.03-1.05), PTFQI (OR: 1.09; 95% CI: 1.06-1.12), TSHI (OR: 1.08; 95% CI: 1.06-1.11), and TT4RI (OR: 1.08; 95% CI: 1.05-1.11). Conversely, the risk of dyslipidemia was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.92-0.97). In stratified analyses, the association between thyroid hormone sensitivity and dyslipidemia was statistically significant for different sexes, glucose levels, and blood pressure states. CONCLUSION: There is a significant association between sensitivity to thyroid hormones and dyslipidemia, regardless of sex, glucose level, or blood pressure. Graphical abstract.

Association of HbA1c with carotid artery plaques in patients with coronary heart disease: a retrospective clinical study.

BACKGROUND AND AIMS: Haemoglobin A1c (HbA1c) levels have been shown to be related to carotid artery plaques. However, studies on the relationship between HbA1c levels and carotid artery plaques in patients with coronary heart disease (CHD) are limited and inconsistent. Our objective was to examine the correlation between HbA1c levels and carotid artery plaques in patients with CHD. METHODS: The study comprised 9275 Chinese adults with CHD from January 1, 2014, to September 30, 2020. HbA1c levels were assessed, and colour Doppler ultrasound was used to evaluate the carotid artery, including plaque presence, intima-media thickness, and plaque echo properties, to investigate the association between HbA1c and carotid plaque. A logistic regression model was used to assess the association between carotid artery plaques, carotid plaque echogenicity, and HbA1c. RESULTS: The HbA1c level of the plaque-present group was higher than that of the plaque-absent group [6.1 (5.6-7.2) vs. 5.8 (5.5-6.5), p < 0.001]. In multiple linear regression analysis, intima-media thickness was associated with HbA1c (p < 0.001). Logistic regression showed that a higher HbA1c level was associated with plaque incidence as well as hyperechoic and heterogeneous plaques (p < 0.001). These associations persist after adjusting for age, sex, blood pressure, lipid profiles, alcohol consumption, and tobacco exposure. CONCLUSION: HbA1c levels are notably associated with carotid artery plaque incidence, intima-media thickness, and plaque echogenicity in patients with CHD. These findings show that different levels of HbA1c may be an indicator for carotid artery plaques and thus, should be observed in patients with CHD.

Relation Between New York Heart Association Functional Class and Remnant Cholesterol, and Non-high Density Lipoprotein Cholesterol in Coronary Heart Disease Patients With Type 2 Diabetes Mellitus.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) are associated with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). However, the association between RC, non-HDL-C, and CHD patients with T2DM has not been comprehensively investigated. We analyzed the association between RC, non-HDL-C, and cardiac function in CHD patients with T2DM. Of the 22 022 CHD patients from six hospitals in Tianjin, 5373 (24.4%) patients with T2DM had higher levels of RC and non-HDL-C (P < .001) than those without T2DM. Among CHD patients with T2DM, RC and non-HDL-C were positively associated with New York Heart Association (NYHA) class Ⅱ [RC: odds ratio (OR), 1.74; 95% confidence interval (CI), 1.50-2.01; P < .01; non-HDL-C: OR, 1.23; 95% CI, 1.15-1.31; P < .01]. After adjusting for confounding factors, this association remained (RC: OR, 1.22; 95% CI, 1.03-1.45; P < .05; non-HDL-C: OR, 1.09; 95% CI, 1.02-1.17; P < .05). These findings provide evidence of an independent positive association between RC, non-HDL-C, and NYHA functional classes. More research is warranted to confirm these findings and determine the mechanisms involved.