Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

Coronary plaque burden predicts perioperative cardiovascular events after coronary endarterectomy.

Background and aims: The risk factors of perioperative and long-term cardiovascular events in patients undergoing coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) are not well determined. This study evaluated the clinical value of coronary plaque burden, coronary anatomic stenosis, and serum biomarkers for predicting perioperative cardiovascular events after off-pump CABG + CE. Methods: This retrospective cohort single-center study enrolled 125 patients undergoing off-pump CABG + CE between February 2018 and September 2021 in China. Coronary plaque burden was reflected by the length of plaque removed by CE. Plaque length-max, which represents the plaque length in patients undergoing single-vessel CE and the maximum plaque length in patients undergoing multivessel CE, was calculated. The primary endpoint was perioperative myocardial infraction (PMI). Results: Plaque length-max was significantly higher in patients with PMI than in those without PMI (2.4 ± 1.5 vs. 1.6 ± 0.9, p = .001). A threshold plaque length-max of 1.15 cm was an independent predictor of PMI (area under the curve: 0.67; sensitivity 87.9%; specificity 59.8%; p = .005). Patients with plaque length-max ≥1.15 had a > 5-fold increase in PMI after adjusting for confounding factors (odds ratio = 5.89; p = .002). Furthermore, interleukin-6 (Beta = .32: p = .028), CD68 (Beta = .34; p = .045), and osteopontin (Beta = .43; p = .008) were significantly correlated with plaque length-max. Conclusions: Plaque length-max was superior to clinical cardiovascular risk factors in predicting PMI occurrence after off-pump CABG + CE, which might be associated with systemic and plaque inflammation state.

Safety and efficacy of microwave ablation for abdominal wall endometriosis: A retrospective study.

Objectives: This retrospective study aimed to evaluate the safety and feasibility of ultrasound-guided microwave ablation in the treatment of abdominal wall endometriosis (AWE). Background: AWE is a rare form of endometriosis that often results in cyclic abdominal pain. The current treatment algorithm for AWE is not well established. Microwave ablation technology is a promising new thermal ablation technique for treating AWE. Methods: This was a retrospective study of nine women with pathologically proven endometriosis of the abdominal wall. All patients were treated with ultrasound-guided microwave ablation. Grey-scale and color Doppler flow ultrasonography, contrast-enhanced ultrasonography, and MRI were used to observe the lesions before and after treatment. The complications, pain relief, AWE lesion volume, and volume reduction rate were recorded 12 months after treatment to evaluate the treatment efficacy. Complications were classified according to the Common Terminology Criteria for Adverse Events and the Society of Interventional Radiology classification system. Results: Contrast-enhanced ultrasound showed that all lesions underwent successful treatment with microwave ablation. The average initial nodule volume was 7.11 ± 5.75 cm3, which decreased significantly to 1.85 ± 1.02 cm3 at the 12-month follow-up with a mean volume reduction rate of 68.77 ± 12.50%. Periodic abdominal incision pain disappeared at 1 month after treatment in all nine patients. The adverse events and complications were Common Terminology Criteria for Adverse Events grade 1 or Society of Interventional Radiology classification grade A. Conclusions: Ultrasound-guided microwave ablation is a safe and effective technique for the treatment of AWE, and further study is warranted.

In Vivo Coronary 18F-Sodium Fluoride Activity: Correlations With Coronary Plaque Histological Vulnerability and Physiological Environment.

BACKGROUND: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque. OBJECTIVES: This prospective study aimed to evaluate the associations between in vivo coronary 18F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary 18F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of 18F-NaF adsorption to vascular microcalcification. METHODS: Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and 18F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary 18F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1ß), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification. RESULTS: A total of 55 specimens were obtained from 42 CAD patients. Coronary 18F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary 18F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1ß expression correlated with coronary 18F-NaF activity (all P < 0.05). No significant association between coronary 18F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05). CONCLUSIONS: Coronary 18F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. 18F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients.

Circulating ADAMTS13 Levels Are Associated with an Increased Occurrence of Obstructive Sleep Apnea.

Background and Aims: Obstructive sleep apnea (OSA) is strongly associated with obesity, metabolic diseases, coronary artery disease (CAD), stroke, hypertension, and other disorders. This study assessed the relationship between circulating a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the presence of OSA. Materials and Methods: This cross-sectional study included a total of 223 patients. We used a powerful high-throughput multiplexed immunobead-based assay to detect circulating levels of ADAMTS13. The associations between circulating ADAMTS13 levels and OSA were evaluated by multivariate logistic regression analysis. Results: Circulating ADAMTS13 levels were significantly elevated in patients with OSA compared with controls (0.8 vs. 2.7 µg/mL, respectively, P < 0.001). After adjusting for confounding factors, circulating ADAMTS13 levels were significantly independently associated with the presence of OSA (odds ratio = 9.96, 95% confidence interval (CI) =4.11-24.13, P < 0.001). Furthermore, circulating ADAMTS13 levels showed discriminatory accuracy in assessing the presence of OSA (area under the curve: 0.87, 95% CI 0.81-0.93, P < 0.001). Conclusion: Circulating ADAMTS13 levels were significantly correlated with the presence of OSA. ADAMTS13 may therefore function as a novel biomarker for monitoring the development and progression of OSA.

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease.

BACKGROUND: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). METHODS: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. RESULTS: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. CONCLUSIONS: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

Assessment of cerebral glucose metabolism in patients with heart failure by 18F-FDG PET/CT imaging.

BACKGROUND: To evaluate the cerebral metabolism in patients with heart failure (HF). METHODS: One hundred and two HF patients were prospectively enrolled, who underwent gated 99mTc-sestamibi single photon emission computed tomography (SPECT)/CT, cardiac and cerebral 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Fifteen healthy volunteers served as controls. Patients were stratified by extent of hibernating myocardium (HM) and left ventricular ejection fraction (LVEF) into 4 groups where Group1: HM < 10% (n = 33); Group2: HM ≥ 10%, LVEF < 25% (n = 34); Group3: HM ≥ 10%, 25% ≤ LVEF ≤ 40% (n = 16) and Group 4: LVEF > 40% (n = 19). The standardized uptake value (SUV) in the whole brain (SUVwhole-brain) and the SUV ratios (SUVR) in 24 cognition-related brain regions were determined. SUVwhole-brain and SUVRs were compared between the 4 patient groups and the healthy controls. RESULTS: SUVwhole-brain (r = 0.245, P = 0.013) and SUVRs in frontal areas, hippocampus, and para-hippocampus (r: 0.213 to 0.308, all P < 0.05) were correlated with HM. SUVwhole-brain differed between four patient groups and the healthy volunteers (P = 0.016) and SUVwhole-brain in Group 1 was lower than that in healthy volunteers (P < 0.05). SUVRs of Group 3 in frontal areas were the highest among four patient subgroups (P < 0.05). CONCLUSIONS: Cerebral metabolism in the whole brain was reduced but maintained in cognition-related frontal areas in HF patients with HM and moderately impaired global left ventricular function.

Thyroid hormones inhibit apoptosis of macrophage induced by oxidized low-density lipoprotein.

Increasing evidence suggests that hypothyroidism aggravates atherosclerosis. Macrophage apoptosis plays a significant role in the development of atherosclerotic plaque. We aimed to explore the effect of thyroid hormones on macrophage apoptosis induced by oxidized low-density lipoprotein (oxLDL). Peripheral blood samples from 20 patients (normal group, hypothyroidism group, coronary artery disease [CAD] group, hypothyroidism + CAD group) were collected to perform messenger RNA microarray analysis. Bioinformatics analysis identified apoptosis and mitogen-activated protein kinase (MAPK) signaling as differentially expressed pathways between CAD and hypothyroidism + CAD group. In vitro, thyroid hormones concentration-dependently promoted cell survival and inhibited apoptosis in oxLDL-treated RAW264.7 macrophages, along with elevated extracellular signal-regulated kinases 1 and 2 (Erk1/2) phosphorylation. The STRING database showed an interaction of thyroid hormone receptor alpha1 (TRα1) and MAPK pathway. TRα1 knockdown increased cell apoptosis and decreased Erk1/2 phosphorylation. Erk1/2 inhibitor aggravated macrophage apoptosis. Moreover, thyroid hormones inhibited oxidative stress in oxLDL-treated macrophages. The study indicates that thyroid hormones concentration-dependently attenuate oxLDL-induced macrophage apoptosis through activating TRα1-Erk1/2 pathway and inhibiting oxidative stress, which implies a potential mechanism of hypothyroid-accelerated atherosclerosis.

The clinical role of combined serum C1q and hsCRP in predicting coronary artery disease.

OBJECTIVE: C1q has been shown to be associated with coronary heart disease (CAD) and can co-deposit with C-reactive protein (CRP) in atherosclerotic plaques. However, few studies have been conducted between C1q, CRP parameters and CAD. The aim of this study is to explore the relationship between C1q and CRP parameters and assess their clinical significance in CAD. METHODS: 238 total patients who underwent coronary artery angiography were enrolled and divided into control group (n = 65), stable CAD group (n = 47) and unstable angina group (UA group, n = 126). Patients' data were collected from self-administered questionnaires and electrical medical records. The severity of coronary stenosis was presented by Gensini score. The relationship between C1q, CRP parameters and CAD were evaluated by multivariate regression analysis and their predicting performance were assessed by ROC analysis and odds ratio analysis. RESULTS: Compared with control group, C1q was showed significantly lower in stable CAD (P = 0.004) and UA groups (P = 0.008), while hsCRP was higher in UA group (P = 0.024). Serum C1q was weakly positively associated with hsCRP (r = 0.24, P < 0.001) but not correlated with Gensini score. Logistic regression identified C1q (OR: 0.87 per 10 mg/L, 95% CI: 0.79-0.95, P = 0.001) and hsCRP (OR: 1.08 mg/L, 95% CI: 1.01-1.15, P = 0.032) as independent determinants of CAD. Furthermore, combined C1q and hsCRP level showed higher discriminatory accuracy in predicting CAD than C1q (AUC: 0.676 vs 0.585, P = 0.101; NRI: 10.4%, P = 0.049; IDI: 3.9%, P < 0.001) or hsCRP (AUC: 0.676 vs 0.585, P = 0.101; NRI: 16.7%, P = 0.006; IDI: 5.8%, P < 0.001). CONCLUSIONS: Reduced serum C1q and increased hsCRP are independently associated with CAD and could be potential predictors for CAD diagnosis. Furthermore, combined C1q and hsCRP showed better performance in predicting CAD than using single one.

TAK1-AMPK Pathway in Macrophages Regulates Hypothyroid Atherosclerosis.

PURPOSE: Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a new therapeutic target. METHODS: We collected peripheral venous blood samples from 20 patients and divided them into 4 groups, namely, the normal group, the HT group, the CAD group and the HT + CAD group. Then we performed mRNA microarray analysis and bioinformatics analysis to screen the differentially expressed genes and pathways, and we also conducted validations on ApoE knockout mice models and Raw264.7 cell models. RESULTS: In short, (1) in the analysis between the CAD group and the HT + CAD group, we found a total of 1218 differentially expressed genes, 11 upregulated pathways and 40 downregulated pathways. (2) We validated that patients with HT and CAD had a significantly decreased expression of MAP3K7 (encoding transforming growth factor-ß-activated kinase 1, TAK1) gene than normal subjects. (3) In animal and cell experiments, we found the decreased expression of TAK1 and the reduced phosphorylation of AMP-activated protein kinase (AMPK) under the hypothyroid and atherosclerotic condition. (4) Changes in the expressions of TAK1 may affect the progression of AS. CONCLUSION: Taken together, these data suggest that the accelerated AS in hypothyroid patients may be due to the suppression of TAK1-AMPK pathway in macrophages. This new finding may become a novel therapeutic target in hypothyroid AS.

Usefulness of Cathepsin S to Predict Risk for Obstructive Sleep Apnea among Patients with Type 2 Diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) was highly prevalent in patients with type 2 diabetes (T2D). Cathepsin S (CTSS), a cysteine protease, is involved in the inflammatory activity in T2D and hypoxia conditions. The aim of the study was to evaluate whether CTSS could be involved in the inflammatory reaction of OSA in patients with T2D. METHODS: We included 158 participants in this study matched for age, gender, and body mass index in 4 groups (control, non-OSA&T2D, OSA&non-T2D, and OSA&T2D). After overnight polysomnography, we collected the clinical data including anthropometrical characteristics, blood pressure, and fasting blood samples in the morning. Plasma CTSS concentration was evaluated using the human Magnetic Luminex Assay. RESULTS: Compared with the control group, both the non-OSA&T2D group and the OSA&non-T2D group showed higher CTSS levels. Plasma CTSS expression was significantly increased in subjects with OSA&T2D compared to subjects with non-OSA&T2D. The OSA&T2D group had higher CTSS levels than the OSA&non-T2D group, but there were no statistically significant differences. Plasma CTSS levels showed significant correlation with the apnea-hypopnea index (AHI) (r = 0.559, P < 0.001) and plasma fasting blood glucose (r = 0.427, P < 0.001). After adjusting confounding factors, plasma CTSS levels were independently associated with the AHI (Beta: 0.386, 95% confidence intervals (CI): 21.988 to 57.781; P < 0.001). Furthermore, we confirmed the higher pinpoint accuracy of plasma CTSS in the diagnosis of OSA (area under the curve: 0.868). CONCLUSIONS: Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D.

EMMPRIN: A potential biomarker for predicting the presence of obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder which is strongly associated with the development of cardiovascular diseases. The aim of the study was to investigate the association between circulating extracellular matrix metalloproteinase inducer (EMMPRIN) and OSA risk. METHODS: This was a cross-sectional study in which a total of 144 patients were recruited. Demographic data, blood biochemical parameters and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously detect circulating levels of EMMPRIN and E-selectin. RESULTS: Circulating levels of EMMPRIN were significantly increased in patients with OSA compared to controls (7.58[6.21-8.80] vs 1.47[0.80-5.91] ng/ml, P < 0.001). After adjusting for confounding factors, we found that circulating EMMPRIN levels were independently associated with the presence of OSA (odds ratio[OR] = 2.240, 95% confidence interval [CI] = 1.391-3.607, P < 0.001). Furthermore, circulating EMMPRIN showed greater discriminatory accuracy in predicting the presence of OSA (AUC:0.904). CONCLUSIONS: Circulating EMMPRIN levels were significantly increased in patients with OSA, and may be a novel marker for predicting the risk of OSA.

CPAP is associated with decreased risk of AF recurrence in patients with OSA, especially those younger and slimmer: a meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is associated with the management of atrial fibrillation (AF). This manuscript aims to discuss the effects of continuous positive airway pressure (CPAP) in patients with rhythm control strategies and patients with different ages, weights and length of follow-up. METHODS: We searched Embase, PubMed, Cochrane, Web of Science and Ovid for relevant studies (from inception to 7 July 2019; English). The primary outcome was documented AF recurrence in CPAP users and nonusers. We assessed pooled data by use of a random-effects model. RESULTS: Nine prospective cohort studies with a total of 2134 participants met the inclusion criteria. Results showed that complementary CPAP therapy reduced AF recurrence (RR = 0.63; 95% CI, 0.56-0.72). In subgroup analyses, the benefits of CPAP were stronger in patients younger than 60 years old (< 60 years old: RR, 0.59; 95% CI, 0.50-0.68 vs. ≥ 60 years old: RR, 0.73; 95% CI, 0.59-0.91), with a body mass index (BMI) of less than 30 (< 30: RR, 0.53; 95% CI, 0.37-0.77 vs. ≥ 30: RR, 0.65; 95% CI, 0.55-0.77) or with less follow-up time (≤ 1 year: RR, 0.57; 95% CI, 0.42-0.79 vs. > 1 year: RR, 0.64; 95% CI, 0.53-0.78). CONCLUSIONS: Complementary CPAP therapy reduces the risk of AF recurrence in OSA patients with rhythm control strategies. In addition to weight control and early AF intervention, CPAP compliance should be recommended along with periodic adjustments as necessary.

The association between circulating APRIL levels and severity of obstructive sleep apnea in Chinese adults.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).

Effects of continuous positive airway pressure on cardiovascular biomarkers in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

PURPOSE: Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP. METHODS: We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus. RESULTS: We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was - 0.64 (95% confidence interval (CI) - 1.19 to - 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P < 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%; P = 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4 h/night. CONCLUSIONS: Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.

TNFRSF11B: A potential plasma biomarker for diagnosis of obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. METHODS: The study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. RESULTS: Our data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). CONCLUSIONS: Plasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.

CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression.

Human glioma-associated mesenchymal stem cells (gbMSCs) are the stromal cell components that contribute to the tumourigenesis of malignant gliomas. Recent studies have shown that gbMSCs consist of two distinct subpopulations (CD90+ and CD90- gbMSCs). However, the different roles in glioma progression have not been expounded. In this study, we found that the different roles of gbMSCs in glioma progression were associated with CD90 expression. CD90high gbMSCs significantly drove glioma progression mainly by increasing proliferation, migration and adhesion, where as CD90low gbMSCs contributed to glioma progression chiefly through the transition to pericytes and stimulation of vascular formation via vascular endothelial cells. Furthermore, discrepancies in long non-coding RNAs and mRNAs expression were verified in these two gbMSC subpopulations, and the potential underlying molecular mechanism was discussed. Our data confirm for the first time that CD90high and CD90low gbMSCs play different roles in human glioma progression. These results provide new insights into the possible future use of strategies targeting gbMSC subpopulations in glioma patients.

Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas.

Glioma, which accounts for more than 30% of primary central nervous system tumours, is characterised by symptoms such as headaches, epilepsy, and blurred vision. Glioblastoma multiforme is the most aggressive, malignant, and lethal brain tumour in adults. Even with progressive combination treatment with surgery, radiotherapy, and chemotherapy, the prognosis for glioma patients is still extremely poor. Compared with the poor outcome and slowly developing technologies for surgery and radiotherapy, the application of targeted chemotherapy with a new mechanism has become a research focus in this field.Moreover, targeted therapy is promising for most solid tumours. The tumour-tropic ability of stem cells, including neural stem cells and mesenchymal stem cells, provides an alternative therapeutic approach. Thus, mesenchymal stem cell-based therapy is based on a tumour-selective capacity and has been thought to be an effective anti-tumour option over the past decades. An increasing number of basic studies on mesenchymal stem cell-based therapy for gliomas has yielded complex outcomes.In this review, we summarise the biological characteristics of human mesenchymal stem cells, and the current status and potential challenges of mesenchymal stem cell-based therapy in patients with malignant gliomas.

[Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein].

It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored. The proliferation, migration and cell aging of macrophages were detected by MTT method, scratch test and ß-galactosidase staining respectively. The ELISA method was used to detect the secretion of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1ß (IL-1ß). Western blot analysis was applied to measure the phosphorylation of focal adhesion kinase (FAK), which was required for the process of proliferation and migration of macrophages. The results showed that oxLDL significantly inhibited the macrophage proliferation and migration, induced cell senescence, and promoted the secretion of TNF-α, MCP-1, and IL-1ß; while T4 reversed those effects of oxLDL on macrophage in a concentration-dependent manner. Moreover, oxLDL increased the phosphorylation of FAK in macrophage, while T4 concentration-dependently reversed the effect. These results suggest that T4 modulates macrophage proliferation, migration, senescence, and secretion of inflammation factors in a concentration-dependent way.

Association between plasma BMP-2 and in-stent restenosis in patients with coronary artery disease.

OBJECTIVE: This study aimed to assess the association between plasma bone morphogenetic protein-2 (BMP-2) level and in-stent restenosis in patients with coronary artery disease. METHODS: A total of 96 patients who underwent percutaneous coronary intervention (PCI) and were followed up after PCI were enrolled in this study. 47 patients diagnosed with in-stent restenosis (ISR) were recruited to ISR group and 49 patients without ISR were recruited to Control group according to the results of coronary angiography (CAG). Baseline characteristic data were collected, and plasma BMP-2 level was evaluated. The results were analyzed using logistic regression. RESULTS: There were 47 patients in the ISR group and 49 patients in the Control group. Plasma levels of BMP-2 were higher in the ISR group than in the non-ISR group [20.96 (18.44, 27.05) pg/ml vs. 29.53 (25.03, 34.07) pg/ml, P<0.01]. Furthermore, the ISR group had significantly longer stent lengths and lower stent diameters than the Control group (P<0.01 and P<0.01, respectively). In multivariate analysis, BMP-2 level, diabetes, stent length and stent diameter were independently associated with ISR [odds ratio (OR)=1.11, 95% confidence interval (CI)=1.03-1.18, P<0.01; OR=4.75, 95% CI=(1.44-15.61), P=0.01; OR=1.06, 95% CI=(1.02-1.11), P<0.01; and OR=0.15, 95% CI=(0.02-0.95), P=0.04, respectively]. CONCLUSIONS: Increased BMP-2 levels were independently associated with ISR in patients with coronary artery disease. Plasma BMP-2 may be useful in predicting ISR.