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1.
Heliyon ; 10(12): e32951, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38988537

ABSTRACT

The use of anti-inflammatory peptides (AIPs) as an alternative therapeutic approach for inflammatory diseases holds great research significance. Due to the high cost and difficulty in identifying AIPs with experimental methods, the discovery and design of peptides by computational methods before the experimental stage have become promising technology. In this study, we present BertAIP, a bidirectional encoder representation from transformers (BERT)-based method for predicting AIPs directly from their amino acid sequence without using any other information. BertAIP implements a BERT model to extract features of a protein, and uses a fully connected feed-forward network for AIP classification. It was constructed and evaluated using the AIP datasets that were reconstructed from the latest Immune Epitope Database. The experimental results showed that BertAIP achieved an accuracy of 0.751 and a Matthews correlation coefficient of 0.451, which were higher than other commonly used methods. The results of the independent test suggested that BertAIP outperformed the existing AIP predictors. In addition, to enhance the interpretability of BertAIP, we explored and visualized the amino acids that the model considered important for AIP prediction. We believe that the BertAIP proposed herein will be a useful tool for large-scale screening and identifying novel AIPs for drug development and therapeutic research related to inflammatory diseases.

2.
Bioresour Technol ; : 131079, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972431

ABSTRACT

The influence of sulfamethoxazole (SMX) on the electrochemical activity, bacterial community, and metabolic state of anode respiring microbes was investigated in constructed-wetland-coupled microbial fuel cells (CW-MFCs). Results suggested that SMX shortened the acclimatisation period and enhanced the maximal power density of the CW-MFC at 0.1 mg/L. Cyclic voltammetry (CV) results indicated that SMX may trigger an electrocatalytic process related to an extra redox-active compound. Exposure to SMX significantly altered the bacterial communities, leading to decreased abundances of Desulfurivibrio and Pseudomonas, while increasing the contents of Rhodobacter and Anaerovorax. Furthermore, metabolites related to amino acids and nucleotide metabolism were suppressed at 10 mg/L SMX, while the related metabolites increased at 0.1 mg/L SMX. The upregulated pathway of biofilm formation indicated that the bacteria tended to form biofilms under the influence of SMX. This study provides valuable insights into the complex interactions between SMX and electrochemically active bacteria.

3.
Cardiovasc Diabetol ; 23(1): 234, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965584

ABSTRACT

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. MATERIALS AND METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression. RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: ß = 0.116; positive remodelling: ß = 0.138; spotty calcification: ß = 0.091; NOS: ß = 0.427; OS: ß = 0.659: SIS: ß = 1.114; SSS: ß = 2.987; PID: ß = 2.716, all P value < 0.001). CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.


Subject(s)
Biomarkers , Cholesterol, LDL , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Plaque, Atherosclerotic , Predictive Value of Tests , Vascular Calcification , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Male , Female , Middle Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Aged , Cholesterol, LDL/blood , Biomarkers/blood , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Vascular Calcification/blood , Risk Factors , Risk Assessment , Dyslipidemias/blood , Dyslipidemias/epidemiology , Dyslipidemias/diagnosis , Retrospective Studies , Coronary Vessels/diagnostic imaging , Severity of Illness Index , Prognosis , Cross-Sectional Studies
4.
Front Cardiovasc Med ; 11: 1372519, 2024.
Article in English | MEDLINE | ID: mdl-38836061

ABSTRACT

Background: The effect of type 2 diabetes mellitus (T2DM) on coronary atherosclerosis detected on coronary computed tomography angiography (CCTA) in hypertensive patients has attracted increasing attention. This study investigated the relationships of T2DM with coronary artery plaque characteristics and semiquantitative CCTA scores in hypertensive patients. Materials and methods: In this single-center study, 1,700 hypertensive patients, including 850 T2DM [HT(T2DM+)] and 850 non-T2DM [HT(T2DM-)] individuals, were retrospectively analyzed after propensity matching. Plaque type, extent, coronary stenosis, segment involvement score (SIS), segment stenosis score (SSS), and CT-based Leaman score (CT-LeSc) based on CCTA were assessed and compared between the two groups. Results: HT(T2DM+) patients had more coronary segments with calcified plaque (2.08 ± 2.20 vs. 1.40 ± 1.91), mixed plaque (2.90 ± 2.87 vs. 2.50 ± 2.66), nonobstructive stenosis (4.23 ± 2.44 vs. 3.62 ± 2.42), and obstructive stenosis (1.22 ± 2.18 vs. 0.78 ± 1.51), a lower proportion of 1-vessel disease (15.3% vs. 25.5%), a higher proportion of 3-vessel disease (59.6% vs. 46.7%), and higher SIS (5.5 ± 3.1 vs. 4.4 ± 3.0), SSS (10.3 ± 8.5 vs. 7.7 ± 7.1), and CT-LeSc (9.4 ± 5.6 vs. 7.9 ± 5.2) than HT(T2DM-) patients (all P-values <0.05). Multivariable analysis revealed that T2DM was an independent risk factor for calcified plaque [odds ratio (OR) = 2.213], obstructive coronary artery disease (CAD) (OR = 1.271), multivessel disease (OR = 1.838), SIS > 4 (OR = 1.910), SSS > 6 (OR = 1.718), and CT-LeSc > 5 (OR = 1.584) in hypertension population (all P-values <0.05). Conclusion: T2DM was independently associated with the presence of calcified coronary artery plaque and increased the risk of obstructive CAD, multivessel disease, and CT-LeSc > 5 in hypertensive patients. More attention should be given to the assessment and management for coronary atherosclerosis in hypertensive patients with T2DM, as this population may have a higher risk of cardiovascular events.

5.
Cardiovasc Diabetol ; 23(1): 217, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915040

ABSTRACT

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.


Subject(s)
Asymptomatic Diseases , Diabetes Mellitus, Type 2 , Diabetic Cardiomyopathies , Diabetic Neuropathies , Magnetic Resonance Imaging, Cine , Predictive Value of Tests , Ventricular Dysfunction, Left , Ventricular Function, Left , Humans , Male , Female , Middle Aged , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetic Neuropathies/physiopathology , Diabetic Neuropathies/diagnostic imaging , Diabetic Neuropathies/etiology , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/epidemiology , Aged , Case-Control Studies , Diabetic Cardiomyopathies/physiopathology , Diabetic Cardiomyopathies/diagnostic imaging , Diabetic Cardiomyopathies/etiology , Risk Factors , Prevalence , Cross-Sectional Studies , Stroke Volume , Myocardial Contraction
6.
J Magn Reson Imaging ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38855837

ABSTRACT

BACKGROUND: The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear. PURPOSE: To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: 352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated. STATISTICAL TEST: Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant. RESULTS: LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (ß = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (ß = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients. DATA CONCLUSION: Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains. TECHNICAL EFFICACY: Stage 3.

7.
J Magn Reson Imaging ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38944678

ABSTRACT

BACKGROUND: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear. PURPOSE: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT). STUDY TYPE: Retrospective. POPULATION: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady state free precession sequence. ASSESSMENT: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated. STATISTICAL TESTS: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant. RESULTS: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (ß = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R2 = 0.627, 0.536, and 0.437 for εs, εe, and εa). DATA CONCLUSION: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

8.
Cardiovasc Diabetol ; 23(1): 210, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902730

ABSTRACT

BACKGROUND: Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. METHODS: A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8-11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. RESULTS: LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P < 0.05). These differences were more obvious in patients with diabetes than those without diabetes. AMI patients with aBGL between 7.8 and 11.1 mmol/L demonstrated significant decreased radial and longitudinal PS, radial PSSR, and radial and longitudinal PDSR than those with aBGL < 7.8 mmol/L (all P < 0.05). AMI patients with aBGL ≥ 11.1 mmol/L showed significantly decreased PS, PSSR and PDSR in all three directions than those with aBGL < 7.8 mmol/L, and decreased longitudinal PSSR than those with aBGL between 7.8 and 11.1 (all P < 0.05). Further, aBGL was significantly and independently associated with radial (ß = - 0.166, P = 0.003) and longitudinal (ß = 0.143, P = 0.008) PS. CONCLUSIONS: Hyperglycemia may exacerbate LV myocardial stiffness in patients experienced first AMI, leading to reduction in LV strains. aBGL was an independent indicator of impaired LV global PS in AMI patients. Blood glucose monitoring is more valuable for AMI patients with diabetes.


Subject(s)
Biomarkers , Blood Glucose , Hyperglycemia , Magnetic Resonance Imaging, Cine , Patient Admission , Predictive Value of Tests , Ventricular Function, Left , Humans , Male , Female , Middle Aged , Hyperglycemia/physiopathology , Hyperglycemia/blood , Hyperglycemia/diagnosis , Hyperglycemia/complications , Aged , Blood Glucose/metabolism , Biomarkers/blood , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/blood , Myocardial Infarction/physiopathology , Myocardial Infarction/complications , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Risk Factors , Retrospective Studies , Biomechanical Phenomena
9.
J Magn Reson Imaging ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703135

ABSTRACT

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

10.
J Environ Manage ; 359: 120943, 2024 May.
Article in English | MEDLINE | ID: mdl-38701583

ABSTRACT

Historical reconstruction of heavy metals (HMs) contamination in sediments is a key for understanding the effects of anthropogenic stresses on water bodies and predicting the variation trends of environmental state. In this work, eighteen sediment cores from the Pearl River Estuary (PRE) were collected to determine concentrations and geochemical fractions of HMs. Then, their potential sources and the relative contributions during different time periods were quantitatively identified by integrating lead-210 (210Pb) radioisotope dating technique into positive matrix factorisation (PMF) method. Pollution levels and potential ecological risks (PERs) caused by HMs were accurately assessed by enrichment factors (EF) based on establishment of their geochemical baselines (GCBs) and multiparameter evaluation index (MPE). HMs concentrations generally showed a particle size- and organic matter-dependent distribution pattern. During the period of 1958-1978, HMs concentrations remained at low levels with agricultural activities and natural processes being identified as the predominant sources and averagely contributing >60%. Since the reform and opening-up in 1978, industrial and traffic factors become the primary anthropogenic sources of HMs (such as Cu, Zn, Cd, Pb, Cr, and Ni), averagely increasing from 22.1% to 28.1% and from 11.6% to 23.4%, respectively. Conversely, the contributions of agricultural and natural factors decreased from 37.0% to 28.5% and from 29.3% to 20.0%, respectively. Subsequently, implementation of environmental preservation policies was mainly responsible for the declining trend of HMs after 2010. Little enrichment of sediment Cu, Zn, Pb, Cr and Ni with EFs (0.15-1.43) was found in the PRE, whereas EFs of Cd (1.16-2.70) demonstrated a slight to moderate enrichment. MPE indices of Cu (50.7-252), Pb (52.0-147), Zn (35.5-130), Ni (19.6-71.5), Cr (14.2-68.8) and Cd (0-9.90) highlighted their potential ecological hazards due to their non-residual fractions and anthropogenic sources.


Subject(s)
Environmental Monitoring , Estuaries , Geologic Sediments , Metals, Heavy , Rivers , Water Pollutants, Chemical , Metals, Heavy/analysis , Risk Assessment , China , Rivers/chemistry , Geologic Sediments/analysis , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis
11.
Article in English | MEDLINE | ID: mdl-38775884

ABSTRACT

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

12.
Br J Dermatol ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820210

ABSTRACT

BACKGROUND: Hypertrophic scar is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation, and existing drugs cannot achieve satisfactory therapeutic effects. OBJECTIVES: This study aimed to explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for hypertrophic scars. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, transforming growth factor ß (TGF-ß) signaling pathway, and other biological pathways. Integrin ß1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib, and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and pro-fibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA (siRNA) can also inhibit mouse scar hyperplasia. CONCLUSIONS: ITGB1 and TGF-ß signaling pathways are important for hypertrophic scar formation. Crizotinib could serve as a potential drug for hypertrophic scars.

13.
J Clin Immunol ; 44(5): 117, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758229

ABSTRACT

AIOLOS, a vital member of the IKAROS protein family, plays a significant role in lymphocyte development and function through DNA binding and protein-protein interactions. Mutations in the IKZF3 gene, which encodes AIOLOS, lead to a rare combined immunodeficiency often linked with infections and malignancy. In this study, we evaluated a 1-year-4-month-old female patient presenting with recurrent infections, diarrhea, and failure to thrive. Laboratory investigations revealed decreased T lymphocyte and immunoglobulin levels. Through whole-exome and Sanger sequencing, we discovered a de novo mutation in IKZF3 (NM_012481; exon 5 c.571G > C, p.Gly191Arg), corresponding to the third DNA-binding zinc finger region of the encoded protein AIOLOS. Notably, the patient with the AIOLOS G191R mutation showed reduced recent thymic emigrants in naïve CD4+T cells compared to healthy counterparts of the same age, while maintaining normal levels of Th1, Th2, Th17, Treg, and Tfh cells. This mutation also resulted in decreased switched memory B cells and lower CD23 and IgM expression. In vitro studies revealed that AIOLOS G191R does not impact the expression of AIOLOS but compromises its stability, DNA binding and pericentromeric targeting. Furthermore, AIOLOS G191R demonstrated a dominant-negative effect over the wild-type protein. This case represents the first reported instance of a mutation in the third DNA-binding zinc finger region of AIOLOS highlighting its pivotal role in immune cell functionality.


Subject(s)
Ikaros Transcription Factor , Mutation , Humans , Ikaros Transcription Factor/genetics , Female , Mutation/genetics , Infant , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/diagnosis , Exome Sequencing , B-Lymphocytes/immunology
14.
J Magn Reson Imaging ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558213

ABSTRACT

BACKGROUND: Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. PURPOSE: To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. STUDY TYPE: Retrospective. POPULATION: Forty-one male patients with ACM and 45 sex- and age-matched controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. ASSESSMENT: Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. RESULTS: Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (ß = 0.614) and circumferential PS (ß = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (ß = -0.631) and LV GLPS (ß = 1.096). DATA CONCLUSION: ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

15.
Cardiovasc Diabetol ; 23(1): 133, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654269

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. MATERIALS AND METHODS: A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS-), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. RESULTS: From controls to the OCAD(MetS-) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p < 0.05). Compared with the OCAD(MetS-) group, the LV GLPS declined significantly (p = 0.027), the LVM increased (p = 0.006), and the LVGFI decreased (p = 0.043) in the OCAD(MetS+) group. After adjustment for covariates in OCAD patients, MetS was an independent factor of decreased LV GLPS (ß = - 0.211, p = 0.002) and increased LVM (ß = 0.221, p = 0.003). The logistic multivariable regression analysis and ROC analysis showed that combined MetS improved the efficiency of predicting LV GLPS reduction (AUC = 0.88) and LVM (AUC = 0.89) increase. CONCLUSIONS: MetS aggravated the damage of LV deformation and function in OCAD patients and was independently associated with LV deformation and impaired LV strain. Additionally, MetS increased the prediction efficiency of increased LVM and decreased LV GLPS. Early detection and intervention of MetS in patients with OCAD is of great significance.


Subject(s)
Metabolic Syndrome , Predictive Value of Tests , Ventricular Dysfunction, Left , Ventricular Function, Left , Humans , Male , Female , Middle Aged , Metabolic Syndrome/physiopathology , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Aged , Case-Control Studies , Risk Assessment , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , Coronary Artery Disease/complications , Magnetic Resonance Imaging, Cine , Risk Factors , Prognosis , Coronary Stenosis/physiopathology , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/complications
16.
Quant Imaging Med Surg ; 14(4): 3018-3032, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38617148

ABSTRACT

Background: Although it is known that mitral regurgitation (MR) in patients with myocardial infarction (MI) may increase the right ventricular (RV) afterload, leading to RV dysfunction, the exact detrimental effects on RV function and myocardial peak strain remain unresolved. In this study, we assessed the impact of MR on the impairment of RV myocardial deformation in patients with MI and explored the independent influential factors of RV peak strain. Methods: A total of 199 MI participants without or with MR were retrospectively assessed in this study. The cardiovascular magnetic resonance examination protocol included a late gadolinium-enhanced (LGE) imaging technique and a cine-balanced steady-state free precession sequence. Statistical tests, including two independent sample t-test or Mann-Whitney U-test, analysis of variance, Kruskal-Wallis test, and multiple linear regression analysis models were performed. Results: The MI (MR+) group exhibited significantly lower RV strain parameters in the radial, circumferential and longitudinal directions when compared to the control and the MI (MR-) groups (both P<0.05). The RV global longitudinal peak strain (GLPS) in the MI group significantly decreased when compared with that in the control group (P<0.05). As moderate-severe MR worsened in patients with MI, RV myocardial global peak strain and the peak systolic strain rate (PSSR) gradually decreased. Multiple linear regression analysis revealed that left ventricular (LV) GLPS, triglycerides, and age were independently correlated with RV GLPS (all P<0.05). RV end-systolic volume (RVESV) acted as an independent association factor for RV global peak strain. Conclusions: MR may exacerbate the impairment of RV peak strain and functions in patients with MI. LV GLPS was positively correlated with RV GLPS. However, RVESV, triglycerides, and age acted as independent risk factors associated with worsening RV GLPS.

17.
J Magn Reson Imaging ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682602

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is associated with worse prognosis in patients with myocardial infarction (MI). However, it is unclear how MetS in MI patients is associated with left atrial (LA) and left ventricular (LV) deformation. PURPOSE: To determine the effect of MetS on LA and LV deformation and atrioventricular interactions in MI patients. STUDY TYPE: Retrospective. POPULATION: One hundred eighty-one MI patients (73 MetS+ and 108 MetS-), 107 age- and sex-matched controls (49 MetS+ and 58 MetS-). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP)/segmented phase-sensitive inversion recovery SSFP sequence. ASSESSMENT: LA strain and strain rates (reservoir, conduit, and active), left atrioventricular coupling index (LACI), and LV geometry and radial, circumferential and longitudinal global peak strains (PS) were compared among groups. STATISTICAL TESTS: Two-way analysis of variance, Spearman and Pearson's correlation coefficients, and multivariable linear regression analysis. P value <0.05 indicated statistical significance. RESULTS: Compared with controls, the MI patients with or without MetS showed impaired LA function (reservoir, conduit, and active) and LV deformation (radial, circumferential, and longitudinal PS) and higher LACI. The MetS+ group had lower LA reservoir and conduit function and LV deformation than MetS- group. The MetS-MI interaction was not statistically significant. Furthermore, multivariable linear regression showed that MetS was independently associated with LA and LV deformation (ß = -0.181 to -0.209) in MI patients; LA function was independently associated with LV circumferential PS (ß = 0.230 to 0.394) and longitudinal PS (ß = 0.189 to 0.420), and LA passive strain and strain rate were negatively associated with LV mass (ß = -0.178 and -0.298). DATA CONCLUSION: MetS may be associated with the LA and LV dysfunction in MI patients. Impaired LV deformation and LV hypertrophy are independently associated with LA dysfunction in MI patients, and the MI patients have higher LACI than controls, suggesting atrioventricular interaction alterations. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

18.
Cardiovasc Diabetol ; 23(1): 148, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685007

ABSTRACT

BACKGROUND: Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. METHODS: A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c < 6.5% (intensive control), HbA1c 6.5-7.5% (modest control), and HbA1c > 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. RESULTS: Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c < 6.5%: hazard ratio (HR) = 2.42, 95% confidence interval (CI) = 1.07-5.45; P = 0.033; HbA1c > 7.5%: HR = 2.24, 95% CI = 1.01-4.99; P = 0.038] and secondary outcomes (HbA1c < 6.5%: HR = 2.84, 95% CI = 1.16-6.96; P = 0.022; HbA1c > 7.5%: HR = 2.65, 95% CI = 1.08-6.50; P = 0.038) compared with those in the middle HbA1c category. CONCLUSIONS: We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.


Subject(s)
Biomarkers , Blood Glucose , Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Glycemic Control , Heart Failure , Predictive Value of Tests , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Humans , Male , Female , Heart Failure/physiopathology , Heart Failure/blood , Heart Failure/diagnostic imaging , Glycated Hemoglobin/metabolism , Middle Aged , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Aged , Blood Glucose/metabolism , Biomarkers/blood , Risk Factors , Retrospective Studies , Magnetic Resonance Imaging, Cine , Time Factors , Hypoglycemic Agents/therapeutic use , Risk Assessment , Prognosis
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 284-288, 2024 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-38448015

ABSTRACT

OBJECTIVE: To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Three GEFS+ probands and their pedigree members presented at the Children's Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants. RESULTS: Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c.1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c.2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c.1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION: The c.1613T>C, c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.


Subject(s)
Epilepsy , Seizures, Febrile , Child , Female , Humans , Infant , Male , China , Mothers , NAV1.1 Voltage-Gated Sodium Channel/genetics , Pedigree , Seizures, Febrile/genetics , Child, Preschool
20.
Cardiovasc Diabetol ; 23(1): 90, 2024 03 06.
Article in English | MEDLINE | ID: mdl-38448890

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique. METHODS: The present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF-), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM. RESULTS: The T2DM(AF+) group was the oldest, had the highest LV end­systolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF-) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF-) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF-) group to the T2DM(AF+) group (all p < 0.001). Compared to the control group, LV PS-circumferential, PSSR-radial and PDSR-circumferential were decreased in the T2DM(AF+) group (all p < 0.001) but preserved in the T2DM(AF-) group. Among all clinical indices, AF was independently associated with worsening LV PS-longitudinal (ß = 2.218, p < 0.001), PS-circumferential (ß = 3.948, p < 0.001), PS-radial (ß = - 8.40, p < 0.001), PSSR-radial and -circumferential (ß = - 0.345 and 0.101, p = 0.002 and 0.014, respectively), PDSR-radial and -circumferential (ß = 0.359 and - 0.14, p = 0.022 and 0.003, respectively). CONCLUSIONS: In patients with T2DM, the presence of paroxysmal AF further exacerbates LV function and deformation. Proactive prevention, regular detection and early intervention of AF could potentially benefit T2DM patients.


Subject(s)
Atrial Fibrillation , Cardiovascular System , Diabetes Mellitus, Type 2 , Humans , Atrial Fibrillation/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Ventricular Function, Left , Magnetic Resonance Spectroscopy
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