Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy ...harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.
Objective
This study aimed to investigate the association between perivascular fat attenuation index (FAI) and hemodynamic significance of coronary lesions.
Methods
Patients with stable angina who ...underwent coronary computed tomography (CT) angiography and invasive fractional flow reserve (FFR) measurement within 2 weeks were retrospectively included. Lesion-based perivascular FAI, high-risk plaque features, total plaque volume (TPV), machine learning–based FFR
CT
, and other parameters were recorded. Lesions with invasive FFR ≤ 0.8 were considered functionally significant.
Results
This study included 167 patients with 219 lesions. Diameter stenosis (DS), lesion length, TPV, and perivascular FAI were significantly larger or longer in the group of hemodynamically significant lesions (FFR ≤ 0.8). In addition, smaller FFR
CT
value was associated with functionally significant lesions (0.720 ± 0.11 vs 0.846 ± 0.10,
p
< 0.001). No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features. According to multivariate analysis, DS, TPV, and perivascular FAI were significant predictors of lesion-specific ischemia. When integrating DS, TPV, and perivascular FAI, the area under the curve (AUC) of this combined method was 0.821, which was similar to that of FFR
CT
(AUC, 0.821 vs 0.850;
p
= 0.426). The diagnostic accuracy of FFR
CT
was higher than that of the combined approach, but the difference was statistically insignificant (79.0% vs 74.0%,
p
= 0.093).
Conclusions
Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions. The combined use of FAI, TPV, and DS could predict ischemic coronary stenosis with high diagnostic accuracy.
Key Points
• Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions.
• Combined use of FAI, plaque volume, and DS provided diagnostic performance comparable to that of machine learning–based FFR
CT
for predicting ischemic coronary stenosis.
• No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features.
Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show ...that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.
Objectives
To investigate the diagnostic performance of absolute myocardial blood flow (MBF), MBF
ratio
, and visual analysis of dynamic CT myocardial perfusion imaging (CT-MPI) for the detection of ...hemodynamically significant coronary stenosis.
Methods
Consecutive patients with chest pain and intermediate-to-high pre-test probability of obstructive coronary artery disease were prospectively enrolled. All patients were referred for dynamic CT-MPI and fractional flow reserve (FFR) measurements within 4 weeks. Absolute MBF, MBF
ratio
(mean MBF of stenosis-subtended territories versus that of reference territories), and visually identified perfusion defect were tested for the diagnostic performance with reference to FFR.
Results
Sixty-two patients with 95 target vessels were included for final analysis. The mean radiation dose for dynamic CT-MPI was 3.0 (2.2–4.0) mSv. The mean lesion-based absolute MBF value was significantly lower in ischemic segments than that in non-ischemic segments (78.0 (65.0–86.0) mL/min/100 mL vs. 133.0 (117.5–163.8) mL/min/100 mL,
p
< 0.001). Similarly, the lesion-based MBF
ratio
was also markedly lower in territories with positive FFR results (0.52 (0.44–0.64) vs. 0.93 (0.91–0.97),
p
< 0.001). According to per-lesion ROC curve analysis, MBF and MBF
ratio
had a similar area under the curve (AUC) for detecting hemodynamically significant lesions (AUC = 0.942 vs. 0.956,
p
= 0.413), which were larger than that of visual analysis (AUC = 0.802, both
p
< 0.01). The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for MBF and 96.1%, 93.2%, and 94.7% for MBF
ratio
.
Conclusions
Absolute MBF and MBF
ratio
had similarly excellent diagnostic performance with reference to FFR. In addition, these two parameters outperformed visual analysis for the detection of myocardial ischemia.
Key Points
• The mean MBF and MBF
ratio
were significantly lower in ischemic segments than those in non-ischemic segments.
•
Absolute MBF and MBF
ratio
had similar AUCs for the detection of hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01).
•
The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBF
ratio
.
Perivascular fat attenuation index (FAI) was thought to be an indicator of active vessel inflammation surrounding coronary plaques. However, whether this index can be reduced by statin treatment ...remains unknown. We aimed to investigate the serial change of lesion-specific perivascular FAI as quantified by coronary computed tomography (CCTA) after statin treatment.
Consecutive patients with chest pain and intermediate likelihood of coronary artery disease were referred for baseline CCTA. Patients were retrospectively included if they were treated medically and underwent follow-up CCTA at 1-year to 1.5-year interval. Lesion-specific perivascular FAI, as well as other plaque features, were measured at baseline and follow-up.
One hundred and eight patients (mean age 67.7 ± 11.1, 76 males) were included. A significant reduction of the FAI value was found for non-calcified plaques and mixed plaques (−68.0 HU ± 8.5 HU Vs. -71.5 HU ± 8.1 HU, p < .001 and − 70.5 HU ± 8.9 HU Vs. -72.8 HU ± 9.0 HU, p = .014). However, this improvement was not observed for calcified plaques (−70.6 HU ± 9.7 HU Vs. −71.7 HU ± 9.9 HU, p = .258). For non-calcified and mixed plaques, the volumes of non-calcified as well as low attenuation component was significantly reduced whereas total plaque volume and volume of calcified component increased. For calcified plaque, total plaque volume also demonstrated remarkable increase after statin treatment
Lesion-specific perivascular FAI decreased at mid-term follow-up after statin treatment for non-calcified and mixed plaques. Perivascular FAI can be a potential imaging biomarker to monitor the anti-inflammation response to statin treatments.
•FAI decreased after statin treatment for non-calcified and mixed plaques.•LAP volume was reduced for non-calcified and mixed plaques.•FAI was not significantly changed for calcified plaques.
The present study aimed to investigate the association between perivascular fat attenuation index (FAI), high-risk plaque features and serum level of high sensitive C-reactive protein (hs-CRP). ...Consecutive patients with intermediate pre-test probability of CAD, who were referred for coronary CT angiography (CCTA), were included. High-risk plaque features were assessed by CCTA and included low attenuation plaque (LAP), positive remodeling (PR), napkin-ring sign (NRS) and spotty calcification. Lesion specific perivascular FAI was also measured for all plaques located on major epicardial vessels with diameter ≧ 2 mm. Laboratory test results, including hs-CRP, were recorded. 199 patients with 260 lesions were finally included. NRS and LAP were more commonly present in the group with elevated hs-CRP (35.9% vs. 19.4% and 14.1% vs. 2.6%, both p < 0.05) and more severe stenosis extent was also noted for this group. However, there was no significant difference between the elevated hs-CRP and normal hs-CRP group with respect to other CT parameters, such as lesion length, PR, spotty calcification and focal calcium score. Perivascular FAI failed to show significant difference between the two groups (− 69.8 ± 10.3HU vs. − 70.0 ± 12.0HU, p = 0.953) and there was poor correlation between perivascular FAI and hs-CRP measurements (r = − 0.04, p = 0.510). In conclusion, LAP and NRS are more commonly present in CAD patients with elevated level of hs-CRP. However, perivascular FAI failed to show such correlation with serum level of hs-CRP.
Objectives
The present study aimed to compare the diagnostic performance of a machine learning (ML)–based FFR
CT
algorithm, quantified subtended myocardial volume, and high-risk plaque features for ...predicting if a coronary stenosis is hemodynamically significant, with reference to FFR
ICA
.
Methods
Patients who underwent both CCTA and FFR
ICA
measurement within 2 weeks were retrospectively included. ML-based FFR
CT
, volume of subtended myocardium (V
sub
), percentage of subtended myocardium volume versus total myocardium volume (V
ratio
), high-risk plaque features, minimal lumen diameter (MLD), and minimal lumen area (MLA) along with other parameters were recorded. Lesions with FFR
ICA
≤ 0.8 were considered to be functionally significant.
Results
One hundred eighty patients with 208 lesions were included. The lesion length (LL), diameter stenosis, area stenosis, plaque burden, V
sub
, V
ratio
, V
ratio
/MLD, V
ratio
/MLA, and LL/MLD
4
were all significantly longer or larger in the group of FFR
ICA
≤ 0.8 while smaller minimal lumen area, MLD, and FFR
CT
value were noted. The AUC of FFR
CT
+ V
ratio
/MLD was significantly better than that of FFR
CT
alone (0.935 versus 0.873,
p
< 0.001). High-risk plaque features failed to show difference between functionally significant and insignificant groups. V
ratio
/MLD-complemented ML-based FFR
CT
for “gray zone” lesions with FFR
CT
value ranged from 0.7 to 0.8 and the combined use of these two parameters yielded the best diagnostic performance (86.5%, 180/208).
Conclusions
ML-based FFR
CT
simulation and V
ratio
/MLD both provide incremental value over CCTA-derived diameter stenosis and high-risk plaque features for predicting hemodynamically significant lesions. V
ratio
/MLD is more accurate than ML-based FFR
CT
for lesions with simulated FFR
CT
value from 0.7 to 0.8.
Key Points
• Machine learning–based FFR
CT
and subtended myocardium volume both performed well for predicting hemodynamically significant coronary stenosis.
• Subtended myocardium volume was more accurate than machine learning–based FFR
CT
for “gray zone” lesions with simulated FFR value from 0.7 to 0.8.
• CT-derived high-risk plaque features failed to correctly identify hemodynamically significant stenosis.
Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury remain elusive. Targeting reactive oxygen species (ROS) provides a practical approach to mitigate myocardial damage ...following reperfusion. In this study, we synthesize an antioxidant nanozyme, equipped with a single-Platinum (Pt)-atom (PtsaN-C), for protecting against I/R injury. PtsaN-C exhibits multiple enzyme-mimicking activities for ROS scavenging with high efficiency and stability. Mechanistic studies demonstrate that the excellent ROS-elimination performance of the single Pt atom center precedes that of the Pt cluster center, owing to its better synergistic effect and metallic electronic property. Systematic in vitro and in vivo studies confirm that PtsaN-C efficiently counteracts ROS, restores cellular homeostasis and prevents apoptotic progression after I/R injury. PtsaN-C also demonstrates good biocompatibility, making it a promising candidate for clinical applications. Our study expands the scope of single-atom nanozyme in combating ROS-induced damage and offers a promising therapeutic avenue for the treatment of I/R injury.
Background
Patients with heart failure (HF) with diabetes may face a poorer prognosis and higher mortality than patients with either disease alone, especially for those in intensive care unit. So ...far, there is no precise mortality risk prediction indicator for this kind of patient.
Method
Two high-quality critically ill databases, the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the Telehealth Intensive Care Unit (eICU) Collaborative Research Database (eICU-CRD) Collaborative Research Database, were used for study participants’ screening as well as internal and external validation. Nine machine learning models were compared, and the best one was selected to define indicators associated with hospital mortality for patients with HF with diabetes. Existing attributes most related to hospital mortality were identified using a visualization method developed for machine learning, namely, Shapley Additive Explanations (SHAP) method. A new composite indicator ASL was established using logistics regression for patients with HF with diabetes based on major existing indicators. Then, the new index was compared with existing indicators to confirm its discrimination ability and clinical value using the receiver operating characteristic (ROC) curve, decision curve, and calibration curve.
Results
The random forest model outperformed among nine models with the area under the ROC curve (AUC) = 0.92 after hyper-parameter optimization. By using this model, the top 20 attributes associated with hospital mortality in these patients were identified among all the attributes based on SHAP method. Acute Physiology Score (APS) III, Sepsis-related Organ Failure Assessment (SOFA), and Max lactate were selected as major attributes related to mortality risk, and a new composite indicator was developed by combining these three indicators, which was named as ASL. Both in the initial and external cohort, the new indicator, ASL, had greater risk discrimination ability with AUC higher than 0.80 in both low- and high-risk groups compared with existing attributes. The decision curve and calibration curve indicated that this indicator also had a respectable clinical value compared with APS III and SOFA. In addition, this indicator had a good risk stratification ability when the patients were divided into three risk levels.
Conclusion
A new composite indicator for predicting mortality risk in patients with HF with diabetes admitted to intensive care unit was developed on the basis of attributes identified by the random forest model. Compared with existing attributes such as APS III and SOFA, the new indicator had better discrimination ability and clinical value, which had potential value in reducing the mortality risk of these patients.
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