A potential early-atheroprotective target: Irgm1 mediates lymphangiogenesis through LEC autophagy by Tfeb translocation.

Lymphatic dysfunction is a pivotal pathological mechanism underlying the development of early atherosclerotic plaques. Potential targets of lymphatic function must be identified to realize the early prevention and treatment of atherosclerosis (AS). The immunity-related GTPase Irgm1 is involved in orchestrating cellular autophagy and apoptosis. However, the effect of Irgm1 on early AS progression, particularly through alterations in lymphatic function, remains unclear. In this study, we confirmed the protective effect of lymphangiogenesis on early-AS in vivo. Subsequently, an in vivo model of early AS mice with Irgm1 knockdown shows that Irgm1 reduces early atherosclerotic plaque burden by promoting lymphangiogenesis. Given that lymphatic endothelial cell (LEC) autophagy significantly contributes to lymphangiogenesis, Irgm1 may enhance lymphatic circulation by promoting LEC autophagy. Moreover, Irgm1 orchestrates autophagy in LECs by inhibiting mTOR and facilitating nuclear translocation of Tfeb. Collectively, these processes lead to lymphangiogenesis. Thus, this study establishes a link between Irgm1 and early AS, thus revealing a novel mechanism by which Irgm1 exerts an early protective influence on AS within the context of lymphatic circulation. The insights gained from this study have the potential to revolutionize the approach and management of AS onset.

Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety.

Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, WDSPE-mPEG2000/Wprodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.

Metabolomic analysis of black sesame seeds: Effects of processing and active compounds in antioxidant and anti-inflammatory properties.

Black sesame seeds (BSS) have been recognized as a functional food due to their nutritional and therapeutic value for many years. In China, BSS is traditionally processed and consumed through two methods, namely, nine steaming nine sun-drying and stir-frying. The present study aimed to evaluate the effects of these processing techniques on the antioxidant and anti-inflammatory activities of BSS. UPLC-QTOF/MS was used for untargeted metabolomics to analyze the composition changes. The results indicated that the different samples had good antioxidant and anti-inflammatory activities, but thermal treatment reduced their activities. Untargeted metabolomics identified a total of 196 metabolites. Molecular docking studies targeting proteins associated with inflammation (iNOS) demonstrated that compounds acting as inhibitors were significantly reduced under both treatments. These results indicate that both nine steaming nine sun-drying and stir-frying lead to substantial loss of antioxidant, anti-inflammatory, and bioactive metabolites in BSS, which provides an important reference for its rational utilization.

Evidential support for garlic supplements against diabetic kidney disease: a preclinical meta-analysis and systematic review.

Garlic (Allium sativum L.) is a popular spice that is widely used for food and medicinal purposes and has shown potential effects on diabetic kidney disease (DKD). Nevertheless, systematic preclinical studies are still lacking. In this meta-analysis and systematic review, we evaluated the role and potential mechanisms of action of garlic and its derived components in animal models of DKD. We searched eight databases for relevant studies from the establishment of the databases to December 2022 and updated in April 2023 before the completion of this review. A total of 24 trials were included in the meta-analysis. It provided preliminary evidence that supplementing with garlic could improve the indicators of renal function (BUN, Scr, 24 h urine volume, proteinuria, and KI) and metabolic disorders (BG, insulin, and body weight). Meanwhile, the beneficial effects of garlic and its components in DKD could be related to alleviating oxidative stress, suppressing inflammatory reactions, delaying renal fibrosis, and improving glucose metabolism. Furthermore, time-dose interval analysis exhibited relatively greater effectiveness when garlic products were supplied at doses of 500 mg kg-1 with interventions lasting 8-10 weeks, and garlic components were administered at doses of 45-150 mg kg-1 with interventions lasting 4-10 weeks. This meta-analysis and systematic review highlights for the first time the therapeutic potential of garlic supplementation in animal models of DKD and offers a more thorough evaluation of its effects and mechanisms to establish an evidence-based basis for designing future clinical trials.

Advancements in Preprocessing and Analysis of Nitrite and Nitrate since 2010 in Biological Samples: A Review.

As a substance present in organisms, nitrite is a metabolite of nitric oxide and can also be ingested. Nitrate is the metabolite of nitrite. Therefore, it is necessary to measure it quickly, easily and accurately to evaluate the health status of humans. Although there have been several reviews on analytical methods for non-biological samples, there have been no reviews focused on both sample preparation and analytical methods for biological samples. First, rapid and accurate nitrite measurement has significant effects on human health. Second, the detection of nitrite in biological samples is problematic due to its very low concentration and matrix interferences. Therefore, the pretreatment plus measuring methods for nitrite and nitrate obtained from biological samples since 2010 are summarized in the present review, and their prospects for the future are proposed. The treatment methods include liquid-liquid microextraction, various derivatization reactions, liquid-liquid extraction, protein precipitation, solid phase extraction, and cloud point extraction. Analytical methods include spectroscopic methods, paper-based analytical devices, ion chromatography, liquid chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography-mass spectrometry and capillary electrophoresis. Derivatization reagents with rapid quantitative reactions and advanced extraction methods with high enrichment efficiency are also included. Nitrate and nitrate should be determined at the same time by the same analytical method. In addition, much exploration has been performed on formulating fast testing through microfluidic technology. In this review, the newest developments in nitrite and nitrate processing are a focus in addition to novel techniques employed in such analyses.

High dietary inflammatory index is associated with decreased plaque stability in patients with coronary heart disease.

Coronary plaque stability is a key pathological mechanism of coronary heart disease (CHD). Inflammation is recognized as a key factor of coronary plaque stability. The dietary inflammatory index (DII) is calculated from 21 dietary nutrients to predict the inflammation potential of an individual's diet. We hypothesized that high DII may be associated with decreased coronary plaque stability in CHD patients; therefore, this study aimed to evaluate the association between DII and plaque stability in patients with CHD. This cross-sectional study included 314 patients with CHD. DII was calculated based on food frequency questionnaires. Plaque stability was measured with optical coherence tomography. The DII ranged from -1.41 to 3.04. After adjusting for confounding factors, higher DII scores were associated with unstable plaque characteristics including thin-capped fibroatheroma (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.78-7.29), macrophage infiltration (OR, 2.16; 95% CI, 1.01-4.61), and plaque rupture (OR, 3.55; 95% CI, 1.73-7.29). Mediation analyses revealed that DII was important mediator of the relationship between plaque stability and food intake including soybeans and nuts, fish and shrimp, eggs (P < .05). The present study confirmed that higher DII is significantly associated with decreased plaque stability in CHD patients, suggesting an important protective role of anti-inflammatory diets in the pathogenesis of CHD.

Assessment on compatibility and safety of labels for pharmaceutical packaging.

Although the secondary packing materials do not directly contact the finished drug products, compound migration may still happen between them. To ensure drug quality and safety, extractables and leachables of the packing materials should be analyzed. In this study, 2,6-di-tert-butyl-4-methylphenol (BHT) was first found in the labels for pharmaceutical packaging. For the identification of the compound, a strategy combining high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy was utilized. Afterwards, a effective and sensitive HPLC method for quantification of BHT was developed and validated. Finally, a toxicological risk assessment of BHT was performed to ensure the safety of drugs.

The combined impact of Type D personality and depression on cardiovascular events after acute myocardial infarction.

BACKGROUND: Type D personality and depression are the independent psychological risk factors for adverse outcomes in cardiovascular patients. The aim of this study was to examine the combined effect of Type D personality and depression on clinical outcomes in patients suffering from acute myocardial infarction (AMI). METHODS: This prospective cohort study included 3568 patients diagnosed with AMI between February 2017 and September 2018. Type D personality and depression were assessed at baseline, while the major adverse cardiac event (MACE) rate (cardiac death, recurrent non-fatal myocardial infarction, revascularization, and stroke) and in-stent restenosis (ISR) rate were analyzed after a 2-year follow-up period. RESULTS: A total of 437 patients developed MACEs and 185 had ISR during the follow-up period. The Type D (+) depression (+) and Type D (+) depression (-) groups had a higher risk of MACE [95% confidence interval (CI) 1.74-6.07] (95% CI 1.25-2.96) and ISR (95% CI 3.09-8.28) (95% CI 1.85-6.22). Analysis of Type D and depression as continuous variables indicated that the main effect of Type D, depression and their combined effect were significantly associated with MACE and ISR. Moreover, Type D (+) depression (+) and Type D (+) depression (-) emerged as significant risk factors for MACE and ISR in males, while only Type D (+) depression (+) was associated with MACE and ISR in female patients. CONCLUSIONS: These findings suggest that patients complicated with depression and Type D personality are at a higher risk of adverse cardiovascular outcomes. Individual assessments of Type D personality and depression, and comprehensive interventions are required.

Relationship between stressful life events and coronary plaque vulnerability among patients with acute coronary syndrome: a moderated mediation model of psychological distress and physiological indices.

We aimed to explore the association between stressful life events and coronary plaque vulnerability, and examine the moderating effects of psychological distress and physiological indices. A total of 311 patients with acute coronary syndrome (ACS) completed Life Events Scale, Zung Self-Rating Depression and Anxiety Scales. Plaque vulnerability was assessed by in vivo optical coherence tomography (OCT). The regression analysis showed that that stressful life events were independent predictors of plaque vulnerability including lipid-rich plaque (OR = 1.018, 95% CI = 1.005, 1.031, p = 0.005), thin-cap fibroatheroma (TCFA) (OR = 1.038, 95% CI = 1.025, 1.051, p < 0.001), rupture (OR = 1.025, 95% CI = 1.013, 1.037, p < 0.001) and thrombus (OR = 1.030, 95% CI = 1.012, 1.048, p = 0.001). The moderated mediation model revealed that there were significant indirect effects of stressful life events on TCFA through total cholesterol, and the path between stressful life events and TCFA can be moderated by depression. Stressful life events increase the risk of vulnerable plaque in ACS patients. The relationship could be moderated by depression and mediated by physiological indices.

Garlic (Allium sativum L.) in diabetes and its complications: Recent advances in mechanisms of action.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia and impaired islet secretion that places a heavy burden on the global health care system due to its high incidence rate, long disease course and many complications. Fortunately, garlic (Allium sativum L.), a well-known medicinal plant and functional food without the toxicity and side effects of conventional drugs, has shown positive effects in the treatment of diabetes and its complications. With interdisciplinary development and in-depth exploration, we offer a clear and comprehensive summary of the research from the past ten years, focusing on the mechanisms and development processes of garlic in the treatment of diabetes and its complications, aiming to provide a new perspective for the treatment of diabetes and promote the efficient development of this field.

Association of Type D personality and mild cognitive impairment in patients with hypertension.

Objective: The aim of this study was to evaluate the association between Type D personality and mild cognitive impairment (MCI) in patients with hypertension. Methods: A total of 324 subjects with hypertension were included in the study. All of them completed questionnaires on demographic characteristics, Type D personality Scale, Montreal Cognitive Assessment (MoCA), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). The Type D personality effect was analyzed as both dichotomous and continuous methods. Results: The incidence of MCI was 56.5% in hypertensive individuals. Type D personality presenting as a dichotomous construct was an independent risk factor of MCI (odds ratio [OR] = 2.814, 95% confidence interval [CI] = 1.577-5.021, p < 0.001), after adjusting for ages, sex and some clinical factors. Meanwhile, main effect of negative affectivity component was independently related to the prevalence of MCI (OR = 1.087, 95%CI = 1.014-1.165, p = 0.019). However, associations between the main effect of social inhibition component (OR = 1.011, 95%CI = 0.924-1.107, p = 0.811) as well as the interaction of negative affectivity and social inhibition (OR = 1.013, 95%CI = 0.996-1.030, p = 0.127) with MCI were not found. Conclusion: The findings suggest that Type D personality is strongly associated with MCI in patients with hypertension. The negative affectivity component of the Type D appears to drive the correlations between Type D and MCI. These findings provide new ideas for studying the mechanisms underlying the relationship between personality and cognitive decline in hypertensive individuals.

The relationship between Type D personality with atherosclerotic plaque and cardiovascular events: The mediation effect of inflammation and kynurenine/tryptophan metabolism.

Purpose: Cardiovascular events and coronary plaque vulnerability are linked to Type D personality. However, the fundamental mechanism has not been clarified. Our study determined to illustrate whether inflammatory status in plasma, in combination with kynurenine pathway activity in Type D individuals, is associated with plaque vulnerability and cardiovascular events in patients with coronary artery disease (CAD). Materials and methods: The Type D personality of 177 CAD patients were evaluated. Plasma biomarkers of inflammation (TNF-α, IL-6, and hs-CRP) were measured and pooled into standardized sumscores. Tryptophan and kynurenine metabolites were measured, and the kynurenine/tryptophan ratio (KTR) was calculated. Plaque vulnerability was measured in vivo by optical coherence tomography. All patients had a follow up of 2 years in which cardiovascular adverse events were recorded. Results: Type D individuals exhibited elevated TNF-α (p = 0.007), IL-6 (p = 0.049), inflammation sumscores (p = 0.002), kynurenine (p = 0.008), and KTR (p = 0.005) than non-Type D group. The serial-multiple mediation showed that the Type D personality with a direct, favorable impact on plaque vulnerability, including thin cap fibroatheroma (TCFA) (point estimate = 0.81; 95% CI = 0.09-1.53), macrophages (point estimate = 0.79; 95% CI = 0.05-1.51), and major adverse cardiac events (MACE) (point estimate = 0.88, 95% CI = 0.08-1.70). In addition, the standardized inflammation sumscores and KTR were mediators of the Type D personality associations with TCFA, macrophages and MACE. Conclusion: These results demonstrated that the connection between Type D personality and poor cardiovascular outcomes in CAD patients can be mediated by pro-inflammatory biomarkers and KTR.

Association Between Dietary Intakes and Plaque Vulnerability Measured by Optical Coherence Tomography in Patients With Coronary Heart Disease: A Mediation Analysis of Inflammatory Factors.

Although studies have proven that diet has a critical role in preventing or delaying atherosclerosis and is far simpler to adjust and adhere to than other risk factors, the underlying mechanisms behind this effect remain not well comprehended. The purpose of this investigation was to determine the impact of inflammatory factors on the connection between dietary ingestion and coronary plaque fragility as measured via optical coherence tomography (OCT) in patients with coronary heart disease (CHD). This research eventually comprised 194 participants with CHD who met the inclusion and exclusion criteria. Semi-quantitative food frequency questionnaire (SQFFQ) was utilized to investigate dietary consumption status, serum levels of inflammatory biomarkers were analyzed using enzyme-linked immunosorbent assay, and OCT was employed to identify the plaque susceptibility of causative lesions in the body. Following correction for statistically meaningful possible confounders in univariate analysis, quartiles of soy and nuts, fruits and vitamin C were negatively associated with coronary plaque vulnerability. Conversely, the upper quartile group of sodium intake had 2.98 times the risk of developing vulnerable plaques compared with the most minimal quartile group. Meanwhile, we observed an inverse dose-response connection between vitamin C consumption and inflammatory biomarkers as well as plaque vulnerability. More importantly, tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6) were significant mediators of the connection between vitamin C and plaque vulnerability, suggesting that vitamin C may inhibit the atherosclerotic inflammatory process by decreasing the expression of IL-6 and TNF-α, thereby reducing the risk of vulnerable plaques. These new findings provide crucial clues to identify anti-inflammatory dietary components as effective therapeutic approaches in the management of CHD, while also providing some insights into their mechanisms of action.

Medical expenditure and its influencing factors of patients with hypertension in Shanxi Province, China: a study based on 'System of Health Accounts 2011' and multiple-layer perceptron neural network.

OBJECTIVES: To study the medical expenditure and influencing factors of patients with hypertension in Shanxi Province, China. DESIGN: A cross-sectional study. SETTING: 1088 medical institutions, including general hospitals, traditional Chinese medicine hospitals, special hospitals, basic medical institutions and public health institutions. PARTICIPANTS: 180 441 hypertensive outpatients and 14 763 inpatients from 1 January to 31 December 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Curative care expenditure for hypertension (CCEht) was measured based on System of Health Accounts 2011. Influenced factors were analysed by univariate analysis and multiple layer perceptron neural network. RESULTS: In 2017, CCEht was US$307.71 million, accounting for 3.63% of total CCE and 0.14% of gross domestic product (GDP) in Shanxi Province of China. CCE of hypertensive outpatients (CCEht-out) and inpatients (CCEht-in) accounted for 44.49% and 55.51% of CCEht. Drug fee accounted for 81.55% of CCEht-out and 22.50% of CCEht-in, respectively. The top three influencing factors were drug fee, surgical fee and hospitalisation days for inpatients, and drug fee, examination fee and test fee for outpatients. CONCLUSIONS: The medical expenditure of hypertension is still heavy for individuals and society. The diagnosis and treatment capacities of primary healthcare system has been enhanced. New rural cooperation medical insurance and urban employee basic medical insurance have a trend of overusing, and the burden of family healthcare expenditure is still heavy. To ease the economic burden of patients with hypertension and improve the efficiency of social resources utilisation, policymakers should pay more attention to key groups, further increase support for primary healthcare system, standardise the treatment and reimbursement of hypertension and incline the reimbursement policy to outpatient service.

Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol.

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1-2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

One-Class Fingerprint Presentation Attack Detection Using Auto-Encoder Network.

Automated Fingerprint Recognition Systems (AFRSs) have been threatened by Presentation Attack (PA) since its existence. It is thus desirable to develop effective presentation attack detection (PAD) methods. However, the unpredictable PAs make PAD be a challenging problem. This paper proposes a novel One-Class PAD (OCPAD) method for Optical Coherence Technology (OCT) images based fingerprint PA detection. The proposed OCPAD model is learned from a training set only consists of Bonafides (i.e. real fingerprints). The reconstruction error and latent code obtained from the trained auto-encoder network in the proposed model is taken as the basis for the following spoofness score calculation. To get more accurate reconstruction error, we propose an activation map based weighting model to further refine the accuracy of reconstruction error. We test different statistics and distance measures and finally use a decision level fusion to make the final prediction. Our experiments are performed using a dataset with 93200 bonafide scans and 48400 PA scans. The results show that the proposed OCPAD can achieve a True Positive Rate (TPR) of 99.43% when the False Positive Rate (FPR) equals to 10% and a TPR of 96.59% when FPR=5%, which significantly outperformed a feature based approach and a supervised learning based model requiring PAs for training.

Robotic-assisted unicompartmental knee arthroplasty: a review.

PURPOSE: Presented here is an up-to-date review concerning robotic-assisted unicompartmental knee arthroplasty (rUKA), including its rationale, operative system, pros and cons. METHODS: We did a systematic research in electronic databases, including PubMed, Cochrane Library, Web of Science, and Embase up to March 30, 2020 to retrieve literature pertaining to rUKA. The search strategies "(robotic* AND knee arthroplasty OR knee replacement)" and "(knee arthroplasty OR knee replacement NOT total)" were used. Studies describing rUKA and clinical trials, dry bone or cadaveric researches regarding technologies, positioning, alignment, function, or survivorship of implants were included in this review. All retrieved studies were first browsed for eligibility on the basis of title and abstract, and the selected studies were further evaluated by reading full text for final inclusion. RESULTS: Robotic-assisted technology has been found to increase the accuracy of bone preparation and implant placement, reduce technical variability and outliers, and enhance reproduction of limb alignment. Additionally, early clinical outcomes were excellent, but mid-term follow-up showed no superiority in component survivorship. The potential drawbacks of the robotic-assisted technology include relatively-low time- and cost-effectiveness, development of some rUKA-related complications, and lack of support by high-quality literature. CONCLUSION: This review shows that rUKA can decrease the number of outliers concerning the optimal implant positioning and limb alignment. However, due to absence of extensive studies on clinical outcomes and long-term results, it remains unclear whether the improved component positioning translates to better clinical outcomes or long-term survivorship of the implant. Nevertheless, since an accurate implant position is presumably beneficial, robotic-assisted technology is worth recommendation in UKA.

Association between food and nutrients intakes and coronary plaque vulnerability in patients with coronary heart disease: An optical coherence tomography study.

BACKGROUND AND AIMS: Dietary intakes play important roles in the prevention and treatment of coronary heart disease (CHD). Coronary plaque vulnerability is the key mechanism leading to CHD progression. We aimed to explore the association between dietary intakes and plaque vulnerability via optical coherence tomography (OCT). METHODS AND RESULTS: A total of 314 CHD patients were included in this study. Dietary intake status was assessed by semi-quantitative food frequency questionnaire and plaque vulnerability was measured by OCT. The results showed that vegetables were negatively associated with macrophage infiltration, thin cap fibroatheroma (TCFA) and thrombus [odds ratio (OR) = 0.48, 0.38, 0.38, 95% confidence interval (95% CI) = 0.24-0.93, 0.17-0.84, 0.15-0.94, all P < 0.05]; fruits were negatively associated with lipid plaque, TCFA, rupture and thrombus (OR = 0.17, 0.11, 0.12, 0.20, 95% CI = 0.07-0.39, 0.04-0.29, 0.05-0.28, 0.08-0.55, all P < 0.05); salt was positively associated with lipid plaque and TCFA (OR = 2.59, 2.83, 95% CI = 1.14-5.90, 1.23-6.51, all P < 0.05). Regarding nutrients intakes, dietary fiber was negatively associated with macrophage infiltration (OR = 0.34, 95% CI = 0.14-0.85, P = 0.021); folate was negatively associated with lipid plaque, TCFA and rupture (OR = 0.22, 0.16, 0.20, 95% CI = 0.09-0.58, 0.06-0.41, 0.08-0.51, all P < 0.05); vitamin C was negatively associated with TCFA, rupture and thrombus (OR = 0.26, 0.22, 0.05, 95% CI = 0.07-0.95, 0.07-0.65, 0.01-0.25, all P < 0.05); sodium was positively associated with lipid plaque, TCFA, rupture and thrombus (OR = 3.43, 3.96, 2.73, 4.84, 95% CI = 1.51-7.80, 1.66-9.45, 1.18-6.27, 1.76-9.28, all P < 0.05). CONCLUSION: Salt and sodium were dietary risk factors for plaque vulnerability, whereas vegetables, fruits, dietary fiber, folate and vitamin C were dietary protective factors for plaque vulnerability.

Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice.

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Metabolomics is a very useful method for investigating the toxicology of drug abuse. We investigated the impact of chronic tramadol administration on the cerebrum of mice, focusing on the metabolites after tramadol administration. The mice received 20 or 50 mg/kg body weight tramadol dissolved in physiological saline daily for 5 weeks via oral gavage. Compared with the control group, the low dose tramadol group showed seven potential biomarkers, including gamma-hydroxybutyric acid, succinate semialdehyde, and methylmalonic acid, which were either up- or down-regulated. Compared with the control group, the high dose tramadol group showed ten potential biomarkers, including gamma-hydroxybutyric acid, glutamine, and O-phosphorylethanolamine, which were either up- or down-regulated. The up-regulated gamma-hydroxybutyric acid and the down-regulated succinate semialdehyde revealed that the neurotransmitter system was disrupted after tramadol abuse. Compared with the low dose tramadol group, there were twenty-nine potential biomarkers in the high dose tramadol group, mainly related to the pentose phosphate pathway and glycerophospholipid metabolism. In conclusion, metabolomics in the tramadol abuse group demonstrated that long-term tramadol abuse can result in oxidative damage, inflammation, and disruption of the GABA neurotransmitter system, which will help to elucidate the toxicology of tramadol abuse.