Development and validation of a nomogram for premature coronary artery disease patients in Guangzhou.

Background: Data regarding risk factors for premature coronary artery disease (PCAD) is scarce given that few research focus on it. This study aimed to develop and validate a clinical nomogram for PCAD patients in Guangzhou. Methods: We recruited 108 PCAD patients (female ≤65 years old and male ≤55 years old) and 96 healthy controls from Sun Yat-sen Memorial Hospital of Sun Yat-sen University between 01/01/2021 and 31/12/2022. Twenty potentially relevant indicators of PCAD were extracted. Next, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. The nomogram was developed based on the selected variables visually. Results: Independent risk factors, including body mass index (BMI), history of PCAD, glucose, Apolipoprotein A1(ApoA1), high density lipoprotein 2-cholesterol (HDL2-C), total cholesterol and triglyceride, were identified by LASSO and logistic regression analysis. The nomogram showed accurate discrimination (area under the receiver operator characteristic curve, ROC, 87.45 %, 95 % CI: 82.58 %-92.32 %). Decision curve analysis (DCA) suggested that the nomogram was clinical beneficial. HDL2, one risk factor, was isolated by a two-step discontinuous density-gradient ultracentrifugation method. And HDL2 from PCAD patients exhibited less 3H-cholesterol efflux (22.17 % vs 26.64 %, P < 0.05) and less delivery of NBD-cholesterol detecting by confocal microscope compared with healthy controls. Conclusions: In conclusion, the seven-factor nomogram can achieve a reasonable relationship with PCAD, and a large cohort were needed to enhance the credibility and effectiveness of our model in future.

The mediation effect of HDL-C: Non-HDL-C on the association between inflammatory score and recurrent coronary events.

Background: Inflammation and lipids are both involved in the pathogenesis of coronary heart disease (CHD). However, the mediation effect of lipoproteins on the association between inflammation and recurrent coronary events in CHD patients remains unclear. Methods: This was a retrospective study including CHD patients hospitalized in the Department of Cardiovascular Medicine in Sun Yat-sen Memorial Hospital between January 2011 and December 2012 with the endpoint of recurrent coronary events. The study calculated inflammatory score based on six serum inflammatory markers, including complement C3, complement C4, hyper-sensitive CRP, fibrinogen, D-dimer, and white blood cell count. Logistic regression analysis, subgroup analysis and mediation analysis were performed to assess the associations between inflammatory score and recurrent coronary events in different subpopulations and the identification of mediators. Inflammatory cytokine expression, cholesterol efflux capacity, and hepatic cholesterol influx were performed in additional CHD patients and healthy controls. Results: There were 191 CHD patients included in the analysis with a median inflammatory score of -0.78 (-2.17, 1.35) and 63 cases of recurrent coronary events. Subgroup logistic regression analysis demonstrated that inflammatory score was positively associated with recurrent coronary events only in the diabetic subgroup [OR: 1.241 (1.004, 1.534), P < 0.046]. HDL-cholesterol (HDL-C): non-HDL-C performed 46.74 % of negative mediation effect on this association. CHD patients had lower cholesterol efflux capacity than healthy controls, which was mediated by HDL: non-HDL ratio of 0.4. No difference was found in hepatic cholesterol influx between the two groups. Conclusion: Inflammatory score was associated with recurrent coronary events mediated by HDL-C: non-HDL-C ratio in diabetic CHD patients, indicating that lipoproteins might aggravate the inflammatory effect on atherosclerosis under hyperglycemia. Our findings suggested that anti-inflammatory and lipid-lowering therapies might be beneficial for this population.

Exploring the efficacy of 18F-FDG PET/CT in hepatocellular carcinoma diagnosis: role of Ki-67 index and tumor differentiation.

PURPOSE: The sensitivity of [18F] fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for detecting hepatocellular carcinoma (HCC) has not been clarified thoroughly. Our study seeks to explore the association between the Ki-67 index and FDG-avidity in HCC tumors using 18F-FDG PET/CT. METHODS: 112 HCC lesions from 109 patients detected by 18F-FDG PET/CT were included retrospectively between August 2017 and May 2022, comprising 82 lesions in the training cohort and 30 in the validation cohort to simulate prospective studies. In the training cohort, lesions were stratified by a lesion-to-liver maximum standardized uptake value (SUVmax) ratio cut-off of 1.59. The relationships between lesion-to-liver SUVmax ratios and several clinical factors including tumor differentiation, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), hepatitis B virus (HBV) infection, Ki-67 index et al. were assessed. These findings were subsequently validated in the independent validation cohort. RESULTS: In the training cohort, group A1 lesions demonstrated a higher Ki-67 index (%, 40.00 [30.00, 57.50] vs. 10.00 [5.00, 28.75], p<0.001) than group A0, the positive correlation between FDG-avidity and Ki-67 index was revealed by multivariate analysis, OR=1.040, 95% CI of OR [1.004-1.077], p=0.030. The calculated cut-off value was 17.5% using the receiver operating characteristic (ROC) curve, with an area under curve (AUC) of 0.834 and 95% CI [0.742-0.926], p<0.001. These findings were further validated in the independent validation cohort, with similar results (AUC=0.875, 95% CI [0.750-1.000], p<0.001). CONCLUSION: In comparison to tumor differentiation, Ki-67 index demonstrates a stronger association with FDG-avidity in HCC tumors, and when the Ki-67 index exceeds 17.5%, 18F-FDG PET/CT might serve as a useful indicator for HCC.

Effects of high-intensity interval training, moderate-intensity continuous training, and guideline-based physical activity on cardiovascular metabolic markers, cognitive and motor function in elderly sedentary patients with type 2 diabetes (HIIT-DM): a protocol for a randomized controlled trial.

Background and objective: Sedentary behavior is of increasing concern in older patients with type 2 diabetes mellitus (T2DM) due to its potential adverse effects on cardiovascular health, cognitive function, and motor function. While regular exercise has been shown to improve the health of individuals with T2DM, the most effective exercise program for elderly sedentary patients with T2DM remains unclear. Therefore, the objective of this study was to assess the impact of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and guideline-based physical activity programs on the cardiovascular health, cognitive function, and motor function of this specific population. Methods: This study will be a randomized, assessor-blind, three-arm controlled trial. A total of 330 (1:1:1) elderly sedentary patients diagnosed with T2DM will be randomly assigned the HIIT group (10 × 1-min at 85-95% peak HR, intersperse with 1-min active recovery at 60-70% peak HR), MICT (35 min at 65-75% peak HR), and guideline-based group (guideline group) for 12 weeks training. Participants in the guideline group will receive 1-time advice and weekly remote supervision through smartphones. The primary outcomes will be the change in glycosylated hemoglobin (HbA1c) and brain-derived neurotrophic factor (BDNF) after 12-weeks. Secondary outcomes will includes physical activity levels, anthropometric parameters (weight, waist circumference, hip circumference, and body mass index), physical measurements (fat percentage, muscle percentage, and fitness rate), cardiorespiratory fitness indicators (blood pressure, heart rate, vital capacity, and maximum oxygen), biochemical markers (high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and HbA1c), inflammation level (C-reactive protein), cognitive function (reaction time and dual-task gait test performance), and motor function (static balance, dynamic balance, single-task gait test performance, and grip strength) after 12 weeks. Discussion: The objective of this study is to evaluate the effect of 12 weeks of HIIT, MICT, and a guideline-based physical activity program on elderly sedentary patients diagnosed with T2DM. Our hypothesis is that both HIIT and MICT will yield improvements in glucose control, cognitive function, cardiopulmonary function, metabolite levels, motor function, and physical fitness compared to the guideline group. Additionally, we anticipate that HIIT will lead to greater benefits in these areas. The findings from this study will provide valuable insights into the selection of appropriate exercise regimens for elderly sedentary individuals with T2DM. Ethics and dissemination: This study has been approved by the Ethics Review Committee of the Reproductive Hospital Affiliated with China Medical University (approval number: 202203). Informed consent will be obtained from all participants or their guardians. Upon completion, the authors will submit their findings to a peer-reviewed journal or academic conference for publication. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200061573.

Proteomic and functional analysis of HDL subclasses in humans and rats: a proof-of-concept study.

BACKGROUND: The previous study investigated whether the functions of small, medium, and large high density lipoprotein (S/M/L-HDL) are correlated with protein changes in mice. Herein, the proteomic and functional analyses of high density lipoprotein (HDL) subclasses were performed in humans and rats. METHODS: After purifying S/M/L-HDL subclasses from healthy humans (n = 6) and rats (n = 3) using fast protein liquid chromatography (FPLC) with calcium silica hydrate (CSH) resin, the proteomic analysis by mass spectrometry was conducted, as well as the capacities of cholesterol efflux and antioxidation was measured. RESULTS: Of the 120 and 106 HDL proteins identified, 85 and 68 proteins were significantly changed in concentration among the S/M/L-HDL subclasses in humans and rats, respectively. Interestingly, it was found that the relatively abundant proteins in the small HDL (S-HDL) and large HDL (L-HDL) subclasses did not overlap, both in humans and in rats. Next, by searching for the biological functions of the relatively abundant proteins in the HDL subclasses via Gene Ontology, it was displayed that the relatively abundant proteins involved in lipid metabolism and antioxidation were enriched more in the medium HDL (M-HDL) subclass than in the S/L-HDL subclasses in humans, whereas in rats, the relatively abundant proteins associated with lipid metabolism and anti-oxidation were enriched in M/L-HDL and S/M-HDL, respectively. Finally, it was confirmed that M-HDL and L-HDL had the highest cholesterol efflux capacity among the three HDL subclasses in humans and rats, respectively; moreover, M-HDL exhibited higher antioxidative capacity than S-HDL in both humans and rats. CONCLUSIONS: The S-HDL and L-HDL subclasses are likely to have different proteomic components during HDL maturation, and results from the proteomics-based comparison of the HDL subclasses may explain the associated differences in function.

Association of Body Mass Index and Abdominal Obesity with Incidence of Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction.

INTRODUCTION: The association between obesity and atrial fibrillation (AF) incidence in heart failure with preserved ejection fraction (HFpEF) patients is currently unclear. Our analyses and results are based on the whole Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial (placebo and spironolactone). METHOD: A total of 2138 subjects without baseline AF were included in the trial. Kaplan-Meier (K-M) curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) were used to assess the incidence of AF with obesity. Of 2138 HFpEF patients without baseline AF, 1165 were obese (body mass index [BMI]≥30 kg/m2). RESULT: The K-M curve showed obese patients developed AF more than overweight (25≤ BMI ≤29.9 kg/m2) patients (p=0.013), confirmed by multivariable analysis, while there's no statistical difference between overweight and normal weight (18.5≤ BMI ≤24.9 kg/m2) patients. The occurrence of AF increased by 3% for every kg/m2 increase in BMI (adjusted HR, aHR: 1.03; 95% CI: 1.00-1.06), with a positive linear association (p for nonlinear: 0.145). Obesity was associated with AF incidence (aHR: 1.62; 95% CI: 1.05-2.50) compared with non-obesity (including overweight and normal-weight patients). CONCLUSION: Abdominal obesity was associated with increased AF incidence (aHR: 1.70; 95% CI: 1.04-2.77), and AF incidence rose by 18% per centimeter in circumference (aHR: 1.18; 95% CI: 1.04-1.34). Obesity and abdominal obesity increase the incidence of AF in HFpEF patients. Further studies need to determine whether there is a difference in AF in response to spironolactone across obese HFpEF pheno groups.

U-shaped association between the triglyceride-glucose index and atrial fibrillation incidence in a general population without known cardiovascular disease.

OBJECTIVE: The triglyceride-glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. METHODS: Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. RESULTS: Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by Kaplan‒Meier curves (P < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80-9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence (P = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. CONCLUSIONS: A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence.

Associations among carotid plaque progression, cerebrovascular/cardiovascular diseases and LDL-C/non-HDL-C goal achievement in diabetic patients: A retrospective cohort study.

BACKGROUND: Impaired glycolipid metabolism can induce vascular injury and plaque formation. It is important to investigate the associations between carotid plaque progression and lipid-lowering goal achievement and cardiovascular disease. METHODS: Diabetic patients who underwent at least 2 carotid ultrasound scans with intervals ≥0.5 years and were hospitalized in the Department of Endocrinology at Sun Yat-sen Memorial Hospital were included. Patients were divided into 3 groups based on carotid plaque progression: the persistent plaque absence, new-onset plaque and persistent plaque presence groups. The primary outcomes were CHD and stroke, while the secondary outcomes were low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal achievement. RESULTS: There were 304 diabetic patients included, with a median follow-up period of 2.15 years. In multivariable logistic regression analysis, persistent plaque presence was positively associated with a 2.285-fold increase in coronary heart disease (CHD) prevalence, while new-onset plaque was associated with a 3.225-fold increase in stroke prevalence compared to persistent plaque absence in patients with follow-up periods ≥ 0.5 years. The association remained significant in patients with a follow-up period ≥ 1 year and ≥2 years. The velocity of average plaque length change was independently associated with increased ΔLDL-C (last - goal) (ß = 0.073, P = 0.048). CONCLUSION: Carotid plaque progression had long-term association with CHD and stroke starting from 0.5 years, while the velocity of average plaque length associated with increased ΔLDL-C (last - goal) might reflect patient response to statins. Repeated carotid plaque measurements might guide lipid-lowering therapies.

Association of motor index scores with fall incidence among community-dwelling older people.

BACKGROUND: Several kinds of motor dysfunction have been studied for predicting future fall risk in community-dwelling older individuals. However, no study has tested the ability of the fine motor index (FINEA) and gross motor index (GROSSA) to predict the risk of falling, as well as the specific fall type. OBJECTIVE: We investigated the associations of FINEA/GROSSA scores with fall risk, explained falls, and unexplained falls. METHODS: A total of 6267 community-dwelling adults aged ≥ 50 years from the Irish Longitudinal Study on Aging (TILDA) cohort were included. First, the associations of FINEA and GROSSA scores with the history of total falls, explained falls and unexplained falls were assessed in a cross-sectional study and further verified in a prospective cohort after 2 years of follow-up by Poisson regression analysis. RESULTS: We found that high FINEA and GROSSA scores were positively associated with almost all fall histories (FINEA scores: total falls: adjusted prevalence ratio [aPR] = 1.28, P = 0.009; explained falls: aPR = 1.15, P = 0.231; unexplained falls: aPR = 1.88, P < 0.001; GROSSA scores: total falls: aPR = 1.39, P < 0.001; explained falls: aPR = 1.28, P = 0.012; unexplained falls: aPR = 2.18, P < 0.001) in a cross-sectional study. After 2 years of follow-up, high FINEA scores were associated with an increased incidence of total falls (adjusted rate ratio [aRR] = 1.42, P = 0.016) and explained falls (aRR = 1.51, P = 0.020) but not with unexplained falls (aRR = 1.41, P = 0.209). High GROSSA scores were associated with an increased incidence of unexplained falls (aRR = 1.57, P = 0.041) and were not associated with either total falls (aRR = 1.21, P = 0.129) or explained falls (aRR = 1.07, P = 0.656). Compared with individuals without limitations in either the FINEA or GROSSA, individuals with limitations in both indices had a higher risk of falls, including total falls (aRR = 1.35, P = 0.002), explained falls (aRR = 1.31, P = 0.033) and unexplained falls (aRR = 1.62, P = 0.004). CONCLUSION: FINEA scores were positively associated with accidental falls, while GROSSA scores were positively associated with unexplained falls. The group for whom both measures were impaired showed a significantly higher risk of both explained and unexplained falls. FINEA or GROSSA scores should be investigated further as possible tools to screen for and identify community-dwelling adults at high risk of falling.

Usefulness of B-Type Natriuretic Peptide for Predicting the Risk of Stroke in Patients With Heart Failure With Preserved Ejection Fraction.

Background B-type natriuretic peptide (BNP) is a well-known biomarker for prognosis in heart failure with patients with preserved ejection fraction. However, the clinical predictive ability of BNP for the risk of stroke in HFpEF is not clear. Methods and Results A total of 799 patients with HFpEF from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial were included. Association of baseline BNP with risk of stroke was assessed using the Cox proportional hazard model. The discriminatory ability of BNP was expressed using the C index. The improvement in 5-year stroke prediction was assessed by C statistic, categorical net reclassification improvement index, and relative integrated discrimination improvement. A total of 34 (4.3%) patients among the 799 patients with HFpEF experienced stroke events over a median of 2.85 years of follow-up. The stroke group showed a higher BNP level than the nonstroke group (375 pg/mL versus 241 pg/mL, respectively; P=0.006). Higher BNP levels were associated with increased risk of stroke after multivariable adjustment (hazard ratio, 3.29 [95% CI, 1.51-7.16]) and had a moderate performance for stroke prediction (C index, 0.67). Adding BNP to CHADS2/CHA2DS2-VASc/R2CHADS2 scores improved their predictive value for stroke (CHADS2: C index, 0.67; BNP+CHADS2: C index, 0.77; net reclassification improvement, 40.9%; integrated discrimination improvement, 3.0%; CHA2DS2-VASc: C index, 0.64; BNP+CHA2DS2-VASc: C index, 0.74; net reclassification improvement, 41.4%; integrated discrimination improvement, 2.2%; R2CHADS2: C index, 0.70; BNP+R2CHADS2: C index, 0.78; net reclassification improvement, 40.9%; integrated discrimination improvement, 3.2%). Conclusions BNP is associated with an increased risk of stroke in patients with HFpEF and may be a valuable biomarker for stroke prediction in HFpEF.

Macrophage-Targeted Sonodynamic/Photothermal Synergistic Therapy for Preventing Atherosclerotic Plaque Progression Using CuS/TiO2 Heterostructured Nanosheets.

Sonodynamic therapy (SDT) and photothermal therapy (PTT) are two effective strategies for the treatment of atherosclerotic plaques. However, the low yield of reactive oxygen species (ROS) of conventional organic sonosensitizers and the low biosafety of hyperthermia limit the therapeutic efficacy of SDT and PTT. Herein, we report copper sulfide/titanium oxide heterostructure nanosheets modified with hyaluronic acid (HA) and PEG (HA-HNSs) for low-intensity sonodynamic and mild-photothermal synergistic therapy for early atherosclerotic plaques. CuS/TiO2 heterostructure nanosheets (HNSs) show high electron-hole separation efficiency and superior sonodynamic performance, because it has high surface energy crystal facets as well as a narrow band. Moreover, HNSs exhibit intense absorbance in the NIR-II region, which endows the nanosheets with excellent photothermal performance. With a further modification of HA, HA-HNSs can selectively target intraplaque proinflammatory macrophages through CD44-HA interaction. Because SDT reduces the expression of heat shock protein 90 and PTT facilitates the sonocatalytic process, the combination of SDT and PTT based on HA-HNSs could synergistically induce proinflammatory macrophage apoptosis. More importantly, the synergistic therapy prevents the progression of early atherosclerotic plaque by removing lesional macrophages and mitigating inflammation. Taken together, this work provides a macrophage-targeting sonodynamic/photothermal synergistic therapy, which is an effective translational clinical intervention for early atherosclerotic plaques.

Central venous pressure and acute kidney injury in critically ill patients with multiple comorbidities: a large retrospective cohort study.

BACKGROUND: Given the traditional acceptance of higher central venous pressure (CVP) levels, clinicians ignore the incidence of acute kidney injury (AKI). The objective of this study was to assess whether elevated CVP is associated with increased AKI in critically ill patients with multiple comorbidities. METHODS: This was a retrospective observational cohort study using data collected from the Medical Information Mart for Intensive Care (MIMIC)-III open-source clinical database (version 1.4). Critically ill adult patients with CVP and serum creatinine measurement records were included. Linear and multivariable logistic regression were performed to determine the association between elevated CVP and AKI. RESULTS: A total of 11,135 patients were enrolled in our study. Critically ill patients in higher quartiles of mean CVP presented greater KDIGO AKI severity stages at 2 and 7 days. Linear regression showed that the CVP quartile was positively correlated with the incidence of AKI within 2 (R2 = 0.991, P = 0.004) and 7 days (R2 = 0.990, P = 0.005). Furthermore, patients in the highest quartile of mean CVP exhibited an increased risk of AKI at 7 days than those in the lowest quartile of mean CVP with an odds ratio of 2.80 (95% confidence interval: 2.32-3.37) after adjusting for demographics, treatments and comorbidities. The adjusted odds of AKI were 1.10 (95% confidence interval: 1.08-1.12) per 1 mmHg increase in mean CVP. CONCLUSIONS: Elevated CVP is associated with an increased risk of AKI in critically ill patients with multiple comorbidities. The optimal CVP should be personalized and maintained at a low level to avoid AKI in critical care settings.

The ratio of the max-to-mean coronary artery calcium score in the most calcified vessel is associated with the presence of coronary artery disease.

PURPOSE: This study aimed to clarify the relationship between the severity of the calcium burden in the most calcified coronary vessel and coronary artery disease (CAD). METHOD: Of 2150 patients, 376 examined by both coronary computed tomographic angiography and invasive coronary angiography (ICA) within 30 days at Sun Yat-sen Memorial Hospital between March 2011 and July 2020 were included. Three coronary artery calcium scores (CACSs), including the Agatston score, volume score, and mass score, and other clinical variables were recorded. The ratio of max-to-mean CACS in the most calcified vessel (CACSmax:mean) was defined as the CACS in the most calcified vessel/average CACS of the four major epicardial coronary arteries. Logistic regression and least absolute shrinkage and selection operator (LASSO) analyses were performed to assess the relationship between CACSmax:mean and CAD. RESULTS: CACSmax:mean was higher in 81.1% of subjects diagnosed with CAD than in subjects without CAD. In multivariate logistic regression analysis, CACSmax:mean determined by the Agatston score, volumetric score, and mass score was associated with CAD. In LASSO analysis, Agatston scoremax:mean (not the total Agatston score or other CACSmax:mean) had the strongest correlation with CAD (ß = 0.125). AUCs in the training set and the validation set were 0.811 and 0.789, respectively. Increased age, diabetes and hypertension correlated with higher Agatston scoremax:mean. CONCLUSIONS: In addition to total CACS, CACSmax:mean may be a novel diagnostic parameter for CAD, showing the calcium burden severity.

IL-6 and IL-8 are likely associated with psychological status in treatment naïve general population.

BACKGROUND: Levels of inflammatory markers are elevated in patients with psychological disorders. However, anti-psychological drugs have an effect on proinflammatory cytokine production and disturb their relationship. Limited evidence focuses on the inflammatory marker profile of psychological status before treatment. This study aimed to investigate the inflammatory biomarker profiles of psychological treatment-naive individuals. METHODS: We included 790 psychological treatment-naive individuals from a longitudinal cohort study of Midlife in the United States (MIDUS). Symptoms of depression, anxiety, and stress were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D) subscales, the Social Anxiety Scale (STAI), and Liebowitz Social Anxiety Scale (LSAS), the Perceived Stress Scale (PSS), respectively. RESULTS: Spearman correlation analysis showed that a higher CESD total score was correlated with higher CRP (p=0.009), IL-6 (p=0.007), fibrinogen (p=0.036), E-selectin (p=0.018), ICAM-1 (p=0.013), and IL-8 (p=0.05) levels. Multivariate linear regression analysis showed that the CESD total score was positively associated with the levels of IL-6 (p=0.024) after adjustments. Moreover, the perceived stress score (PSS) was negatively associated with the levels of IL-8 (p=0.025). However, these associations were not significant after multiple testing (p=0.088, 0.091, respectively). LIMITATIONS: The casual relationship cannot be drawn due to the cross-sectional design CONCLUSION: Overall, our results suggested IL-6 and IL-8 might play a important role in the pathogenesis of psychological disorder. Larger and longitude studies are needed to confirm our results.

Insulin Rescued MCP-1-Suppressed Cholesterol Efflux to Large HDL2 Particles via ABCA1, ABCG1, SR-BI and PI3K/Akt Activation in Adipocytes.

PURPOSE: Intracellular cholesterol imbalance plays an important role in adipocyte dysfunction of obesity. However, it is unclear whether obesity induced monocyte chemoattractant protein-1 (MCP-1) causes the adipocyte cholesterol imbalance. In this study, we hypothesize that MCP-1 impairs cholesterol efflux of adipocytes to HDL2 and insulin rescues this process. METHODS: We recruited coronary artery disease (CAD) patients with obesity and overweight to analyze the association between MCP-1 and HDL2-C by Pearson correlation coefficients. We performed [3H]-cholesterol efflux assay to demonstrate the effect of MCP-1 and insulin on cholesterol efflux from 3T3-L1 adipocytes to large HDL2 particles. Western blot, RT-qPCR, cell-surface protein assay, and confocal microscopy were performed to determine the regulatory mechanism. RESULTS: Plasma MCP-1 concentrations were negatively correlated with HDL2-C in CAD patients with obesity and overweight (r = -0.60, p < 0.001). In differentiated 3T3-L1 adipocytes, MCP-1 reduced cholesterol efflux to large HDL2 particles by 55.4% via decreasing ATP-binding cassette A1 (ABCA1), ABCG1, and scavenger receptor class B type I (SR-BI) expression. Intriguingly, insulin rescued MCP-1 mediated-inhibition of cholesterol efflux to HDL2 in an Akt phosphorylation-dependent manner. The rescue efficacy of insulin was 138.2% for HDL2. Moreover, insulin increased mRNA and protein expression of ABCA1, ABCG1, and SR-BI at both transcriptional and translational levels via the PI3K/Akt activation. CONCLUSIONS: These findings indicate that MCP-1 impairs cholesterol efflux to large HDL2 particles in adipocytes, which is reversed by insulin via the upregulation of ABCA1, ABCG1, and SR-BI. Therefore, insulin might improve cholesterol imbalance by an anti-inflammatory effect in adipocytes. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000033297; Date of registration: 2020/05/ 27; Retrospectively registered.

LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes.

BACKGROUND: Fibroblast-like synoviocytes (FLSs), which can migrate and directly invade the cartilage and the bone, are crucial players in joint damage in rheumatoid arthritis (RA). Nevertheless, the detailed mechanisms underlying the aberrant activation of RA FLSs remain unclear. Several studies have attempted to explore the relationship between long non-coding RNAs (lncRNAs) and RA pathology; however, the role of lncRNAs in RA is unknown. The present study aimed to determine the functions of tumor necrosis factor-α and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory lincRNA (THRIL) in RA FLSs migration and invasion. METHODS: Small interfering RNA targeting THRIL or lentivirus overexpressing THRIL was used to knockdown or overexpress THRIL. Quantitative reverse transcription polymerase chain reaction (PCR) was employed for the detection of RNA expression. The proliferation rate of RA FLSs was measured using a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Migration and invasion were detected using a transwell chamber. Downstream targets were identified using a human cell cycle real-time PCR array and a human cell motility real-time PCR array. RESULTS: A significant decrease in THRIL expression was found in RA FLSs compared with cells from healthy control (HC)patients. THRIL is mainly localized in the nucleus. Knockdown of THRIL increased the proliferation, migration, and invasion of RA FLSs. In contrast, THRIL overexpression had the opposite effect. THRIL knockdown increased interleukin-1ß (IL-1ß)-triggered expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. THRIL overexpression led to a significant decrease in MMP-13 expression in response to stimulation with IL-1ß. Furthermore, we observed that the expression levels of cyclin-dependent kinase 1 (CDK1) and G2 and S phase-expressed-1 (GTSE1), both of which are associated with cellular mobility and proliferation, were downregulated with THRIL overexpression. CONCLUSIONS: Reduced expression of lncRNA THRIL represses the proliferation, migration, and invasion of RA FLSs, suggesting that lncRNA THRIL might be a potential target for RA therapy.

Is 18F-FDG PET/CT Beneficial for Newly Diagnosed Breast Cancer Patients With Low Proportion of ER Expression?

OBJECTIVE: It is unclear whether the receptor status of breast malignancy or the proportion of receptors expression is useful in the interpretation of 18F-FDG PET/CT. This study's purpose was to analyze whether 18F-FDG PET/CT was valuable for helping newly diagnosed breast cancer patients find suspected or unsuspected metastasis lesions based on the proportion of receptors expression. MATERIALS AND METHODS: Eighty newly diagnosed breast cancer patients were divided into six groups, containing N0 (no extraaxillary lymph node metastasis), N1 (extraaxillary lymph node metastasis), M0 (no distant metastasis), and M1 (distant metastasis) groups, C0 (no unsuspected metastasis), and C1 (unsuspected metastasis and treatment plan changed) detected by PET/CT. The main data, including the proportion of receptors ER (estrogen receptor), PR (progesterone receptor), and Her-2 (human epidermal growth factor receptor 2) status, were extracted. Simple correlation and logistic regression were preformed to analyze the association between them. RESULTS: Patients in N1 group had lower proportion of ER (%) and PR (%) than that in N0 group (ER: 2 [0-80] vs. 80 [15-95]; PR: 1 [0-10] vs. 20 [0-45], p<0.001). Moreover, the proportions of ER and PR were negatively correlated with N1 (ER: [r= -0.339, p= 0.002], PR: [r= -0.247, p= 0.011]) by simple correlation. Also, patients in C1 group had lower proportion of ER (%) and PR (%) than those in C0 group (ER: 10 [0-85] vs. 80 [15-90], p=0.026; PR: 1 [0-10] vs. 20 [0-70], p=0.041), while the distribution of ER and PR between M1 and M0 group had no significant difference. After the adjustment of traditional factors, the negative correlation between the proportion of ER (OR=0.986, 95% CI of OR [0.972-0.999], p=0.016) and C1 was found by logistic regression, cutoff value was 25% (ER) calculated by ROC (Receiver Operating Characteristic) curve (AUC [Area Under Curve]= 0.647, p=0.024). CONCLUSION: The proportion of ER in newly diagnosed breast cancer was negatively correlated with unsuspected metastasis detected by 18F-FDG PET/CT. 18F-FDG PET/CT might be recommended for newly diagnosed breast cancer patients with single lesions when the ER expression proportion is less than 25% to find unsuspected metastasis lesions and to modify treatment plan contrasted with conventional imaging and clinical examination.

Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.

Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI). Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-ß1 (TGF-ß1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot. Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF. Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.

No Sex Differences in Psychological Burden and Health Behaviors of Healthcare Workers During the COVID-19 Stay-at-Home Orders.

Background: Females with novel coronavirus disease 2019 (COVID-19) state-ordered home isolation were associated with higher anxiety and reduced sleep quality than males. Sex differences in psychobehavioral changes during the COVID-19 stay-at home orders among healthcare workers remained unclear. The purpose of this study was to explore the sex differences in psychological burden and health behaviors among these persons. Methods: This was a cross-sectional study using online data available in the open Interuniversity Consortium for Political and Social Research (OPENICPSR). Healthcare workers including females and males who transitioned to working from home during the COVID-19 stay-at-home orders were included. Sex differences were compared using the chi-square test and Student's t-test. We performed logistic and linear regression analyses to determine the association of females with psychological burden and health behaviors. Results: A total of 537 respondents (425 females and 112 males) were enrolled in our study. Sex differences in age (42.1 ± 12.3 years vs. 46.6 ± 15.7 years, t = -2.821, p = 0.005), occupation (χ2 = 41.037, p < 0.001), mood change (n = 297, 69.9% vs. n = 61, 54.5%, χ2 = 9.482, p = 0.002), bedtime schedule (χ2 = 6.254, p = 0.044) and news consumption (n = 344, 80.9% vs. n = 76, 67.9%, χ2 = 8.905, p = 0.003) were statistically significant. Logistic regression showed that females was negatively associated with better mood status (OR = 0.586, 95% CI 0.153-2.247, p = 0.436). In addition, linear regression showed that females were not correlated with total sleep time after adjusting for sio-demographics, mental health outcomes and health behaviors (B = 0.038, 95% CI -0.313-0.388, p = 0.833). Conclusion: No sex differences in psychological burden and health behaviors of healthcare workers were found during the COVID-19 stay-at-home orders. The COVID-19 state-ordered home isolation may be a potential way to reduce disproportionate effects of COVID-19 pandemic on females and help to minimize sex differences in psychological burden and health behaviors among healthcare workers.

Efficacy and Safety of High-Density Lipoprotein/Apolipoprotein A1 Replacement Therapy in Humans and Mice With Atherosclerosis: A Systematic Review and Meta-Analysis.

Background: Although elevation of HDL-C levels by pharmaceutical drugs have no benefit of cardiovascular endpoint, the effect of high-density lipoprotein/apolipoprotein A1 (HDL/apoA-1) replacement therapy on atherosclerosis is controversial. The current meta-analysis analyzed the effects of HDL/apoA-1 replacement therapies on atherosclerotic lesions both in humans and mice. Methods: The PubMed, Cochrane Library, Web of Science, and EMBASE databases were searched through June 6, 2020. The methodological quality of the human studies was assessed using Review Manager (RevMan, version 5.3.). The methodological quality of the mouse studies was assessed using a stair list. STATA (version 14.0) was used to perform all statistical analyses. Results: Fifteen randomized controlled human trials and 17 animal studies were included. The pooled results showed that HDL/apoA-1 replacement therapy use did not significantly decrease the percent atheroma volume (p = 0.766) or total atheroma volume (p = 0.510) in acute coronary syndrome (ACS) patients (N = 754). However, HDL/apoA-1 replacement therapies were significantly associated with the final percent lesion area, final lesion area, and changes in lesion area (SMD, -1.75; 95% CI: -2.21~-1.29, p = 0.000; SMD, -0.78; 95% CI: -1.18~-0.38, p = 0.000; SMD: -2.06; 95% CI, -3.92~-0.2, p = 0.03, respectively) in mice. Conclusions: HDL/apoA-1 replacement therapies are safe but do not significantly improve arterial atheroma volume in humans. The results in animals suggest that HDL/apoA-1 replacement therapies decrease the lesion area. Additional studies are needed to investigate and explain the differences in HDL/apoA-1 replacement therapy efficacies between humans and animals. Trial registration number: Human pooled analysis: PROSPERO, CRD42020210772. prospectively registered.