Coronary artery calcification burden, atherogenic index of plasma, and risk of adverse cardiovascular events in the general population: evidence from a mediation analysis.

BACKGROUND: Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). METHODS: This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants' CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. RESULTS: During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32-1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). CONCLUSIONS: An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

3,3'-Diindolylmethane induces ferroptosis by BAP1-IP3R axis in BGC-823 gastric cancer cells.

To investigate the effect and potential mechanism of 3,3'-diindolylmethane (DIM) on ferroptosis against gastric cancer, cells proliferation, lipid reactive oxygen species (ROS) and GSH level were measured in the BGC-823 gastric cancer cells after DIM treatment. Western blotting was used to detect the expression of SLC7A11, GPX4, IP3R and BAP1. Results showed that DIM could induce ferroptosis in the BGC-823 gastric cancer cells via upregulating lipid-ROS level and decreasing GSH generation. Besides, DIM also significantly reduced the protein level of SLC7A11 and GPX4, which was an important regulator of ferroptosis. In addition, DIM promoted the protein level of BAP1 and IP3R in a concentration-dependent manner in the BGC-823 gastric cancer cells. The knockdown of BAP1 could reduce IP3R level and DIM-induced ferroptosis of gastric cancer cells. Taken together, these results indicated that DIM could induce ferroptosis to exert anti-cancer effects via BAP1-IP3R axis, suggesting its effective therapeutic potential in gastric cancer.

Early extremity MRI findings and pathological synovial changes in antigen-induced arthritis rabbit model.

PURPOSE: To investigate the association between early extremity MRI (E-MRI) findings and synovial pathological changes in antigen-induced arthritis (AIA) rabbit model. MATERIALS AND METHODS: AIA was successfully induced in the right knee of 32 sensitized Japanese white rabbits, which were then divided into four groups according to the time of killing after AIA induction: 1-week (Group A), 2-weeks (Group B), 3-weeks (Group C), and 4-weeks (Group D); the left knee served as control in each rabbit. RESULTS: There were varying degrees of joint effusion in all AIA groups. E-MRI scan showed low signal in T1-weighted images (T1Wi) and high signal in T2-weighted images (T2Wi). Enhanced E-MRI revealed elevated synovial signal at the right knee in the three-dimensional spoiled gradient T1WI, showing linear and band-shaped, diffuse hyperintensity. Histological examination of right knees found scattered inflammatory cell infiltration, swelling, and proliferation of the synovial cells at 7 days after AIA induction and dispersed and disordered proliferation of synovial cells up to 3 layers at 28 days postinduction. The synovial enhancement of right knee E-MRI was consistent with a synovial pathology score for all rabbits (Kappa = 0.965, P < 0.01). CONCLUSION: E-MRI can reveal the degree of changes in the joints and synovium at different periods of the AIA model.

Effects of Different Carbohydrate Content Diet on Gut Microbiota and Aortic Calcification in Diabetic Mice.

Introduction: Vascular calcification is a major cause of cardiovascular accidents in patients with type 2 diabetes mellitus. This study aimed to investigate the impact of carbohydrates on gut microbiota and aortic calcification in diabetic ApoE-/- mice. Methods: The diabetic ApoE-/- mice were randomly divided into 4 groups: ketogenic diet group, low carbohydrate diet group, medium carbohydrate diet group, and high carbohydrate diet group. The mice were fed continuously for 6 months, with blood glucose, blood ketone and body weight monitored monthly. Lipid metabolism indicators and inflammatory factors were detected using ELISA. The intestinal barrier, atherosclerotic lesion areas, and vascular calcifications were analyzed based on their morphology. Gut microbiota was analyzed using 16S rRNA genes. Results: We found that ketogenic diet played some roles improving glucose, lipid metabolism, and inflammation. Ketogenic diet could improve the intestinal barrier to some extent and increase intestinal bacteria. Compared to the other three groups, the relative abundance of genus Allobaculum, species Blautia producta and Clostridium Ramosum in the ketogenic diet group was significantly increased (P <0.05), which has protective effects in diabetic ApoE-/- mice. Conclusion: Ketogenic diet could delay the onset of aortic atherosclerosis, aortic calcification and improve intestinal barrier function in diabetic ApoE-/- mice.

Advances in positron emission tomography tracers related to vascular calcification.

Microcalcification, a type of vascular calcification, increases the instability of plaque and easily leads to acute clinical events. Positron emission tomography (PET) is a new examination technology with significant advantages in identifying vascular calcification, especially microcalcification. The use of the 18F-NaF is undoubtedly the benchmark, and other PET tracers related to vascular calcification are also currently in development. Despite all this, a large number of studies are still needed to further clarify the specific mechanisms and characteristics. This review aimed at providing a summary of the application and progress of different PET tracers and also the future development direction.

Quantitative Susceptibility Mapping of Brain Iron Deposition in Patients With Recurrent Depression.

OBJECTIVE: Recurrence is the most significant feature of depression and the relationship between iron and recurrent depression is still lack of direct evidence in vivo. METHODS: Twenty-one patients with depression and twenty control subjects were included. Gradient-recalled echo, T1 and T2 images were acquired using a 3.0T MRI system. After quantitative susceptibility mapping were reconstructed and standardized, a whole-brain and the regions of interest were respectively analyzed. RESULTS: Significant increases in susceptibility were found in multiple recurrent depression patients, which involved several brain regions (frontal lobes, temporal lobe structures, occipital lobes hippocampal regions, putamen, thalamus, cingulum, and cerebellum). Interestingly, no susceptibility changes after treatment compared to pre-treatment (all p>0.05) and no significant correlation between susceptibility and Hamilton Depression Rating Scale were found. Besides, it was close to significance that those with a higher relapse frequency or a longer mean duration of single episode had a higher susceptibility in the putamen, thalamus, and hippocampus. Further studies showed susceptibility across the putamen (ρ2=0.27, p<0.001), thalamus (ρ2=0.21, p<0.001), and hippocampus (ρ2=0.19, p<0.001) were strongly correlated with total course of disease onset. CONCLUSION: Brain iron deposition is related to the total course of disease onset, but not the severity of depression, which suggest that brain iron deposition may be a sign of brain damage in multiple recurrent depression.

Advances in CT Techniques in Vascular Calcification.

Vascular calcification, a common pathological phenomenon in atherosclerosis, diabetes, hypertension, and other diseases, increases the incidence and mortality of cardiovascular diseases. Therefore, the prevention and detection of vascular calcification play an important role. At present, various techniques have been applied to the analysis of vascular calcification, but clinical examination mainly depends on non-invasive and invasive imaging methods to detect and quantify. Computed tomography (CT), as a commonly used clinical examination method, can analyze vascular calcification. In recent years, with the development of technology, in addition to traditional CT, some emerging types of CT, such as dual-energy CT and micro CT, have emerged for vascular imaging and providing anatomical information for calcification. This review focuses on the latest application of various CT techniques in vascular calcification.

Research Progress of Imaging Methods for Detection of Microvascular Angina Pectoris in Diabetic Patients.

Diabetes is a complex metabolic disease characterized by hyperglycemia. Its complications are various, often involving the heart, brain, kidney, and other essential organs. At present, the number of diabetic patients in the world is growing day by day. The cardiovascular disease caused by diabetes has dramatically affected the quality of life of diabetic patients. It is the leading cause of death of diabetic patients. Diabetic patients often suffer from microvascular angina pectoris without obstructive coronary artery disease. Still, there are typical ECG ischemia and angina pectoris, that is, chest pain and dyspnea under exercise. Unlike obstructive coronary diseases, nitrate does not affect chest pain caused by coronary microvascular angina in most cases. With the increasing emphasis on diabetic microvascular angina, the need for accurate diagnosis of the disease is also increasing. We can use SPECT, PET, CMR, MCE, and other methods to evaluate coronary microvascular function. SPECT is commonly used in clinical practice, and PET is considered the gold standard for non-invasive detection of myocardial blood flow. This article mainly introduces the research progress of these imaging methods in detecting microvascular angina in diabetic patients.

The evaluation of anti-angiogenic effects of Endostar on rabbit VX2 portal vein tumor thrombus using perfusion MSCT.

BACKGROUND: There were many treatments for hepatocellular carcinoma with portal vein tumor thrombus (PVTT), in which targeted anti-angiogenic drug therapy is becoming a popular research topic. However, an objective and non-invasive method that can evaluate the treatment effects is still lacking. METHODS: Eighteen New Zealand white rabbits implanted with VX2 tumor thrombus in portal vein were randomly assigned into 3 groups: Endostar, saline, or control, six in each group. Multi-slice CT (MSCT) perfusion scanning was performed to measure the differences in blood flow (TBF), tissue blood volume (TBV), and capillary permeability time the surface (PS) before and after Endostar treatment, between Endostar and saline treatment. Two weeks after treatment, both Endostar and saline groups underwent CT perfusion scan. The rabbits then were sacrificed by air embolism, and specimens of tumor thrombosis were collected. Immunohistochemistry assay was also performed to compare the expression of vascular endothelial growth factor (VEGF) in PVTT after Endostar, saline and placebo treatment. RESULTS: In Endostar group, PVTT CT perfusion parameters (TBF, TBV, PS) significantly decreased after the treatment (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were significantly lower in Endostar group than in Saline group (p <0.05). VEGF is mainly expressed in cytoplasma. After Endostar treatment, the expression of VEGF in PVTT was markedly reduced. There was also significant difference on post-treatment VEGF protein expression measured by Immunohistochemistry assay between Endostar group and control group (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were positively correlated with VEGF protein expression in all 3 groups (rs > 0, p <0.05). CONCLUSIONS: Multi-slice CT perfusion imaging can evaluate the anti-angiogenic effects of Endostar for the VX2 tumor thrombus in portal vein, and provide quantitative functional information.

Clinical study of tumor angiogenesis and perfusion imaging using multi-slice spiral computed tomography for breast cancer.

OBJECTIVES: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP- 2) in breast cancer. METHODS: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. RESULTS: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). CONCLUSION: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.