[Association between body composition and coronary artery calcification in patients with chronic kidney disease].

Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

A deep-learning model using enhanced chest CT images to predict PD-L1 expression in non-small-cell lung cancer patients.

AIM: To develop a deep-learning model using contrast-enhanced chest computed tomography (CT) images to predict programmed death-ligand 1 (PD-L1) expression in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Preoperative enhanced chest CT images and immunohistochemistry results for PD-L1 expression (<1% and ≥1% were defined as negative and positive, respectively) were collected retrospectively from 125 NSCLC patients to train and validate a deep-learning radiomics model (DLRM) for the prediction of PD-L1 expression in tumours. The DLRM was developed by combining the deep-learning signature (DLS) obtained from a convolutional neural network and clinicopathological factors. The indexes of the area under the curve (AUC), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the efficiency of the DLRM. RESULTS: DLS and tumour stage were identified as independent predictors of PD-L1 expression by the DLRM. The AUCs of the DLRM were 0.804 (95% confidence interval: 0.697-0.911) and 0.804 (95% confidence interval: 0.679-0.929) in the training and validation cohorts, respectively. IDI analysis showed the DLRM had better diagnostic accuracy than DLS (0.0028 [p<0.05]) in the validation cohort. Additionally, DCA revealed that the DLRM had more net benefit than the DLS for clinical utility. CONCLUSION: The proposed DLRM using enhanced chest CT images could function as a non-invasive diagnostic tool to differentiate PD-L1 expression in NSCLC patients.

[Diagnostic value of combining serum soluble ST2 and interleukin-33 for heart failure patients with preserved left ventricular ejection fraction].

Objective: Diagnostic efficacy of serum markers is low for heart failure patients with preserved left ventricular ejection fraction (HF-pEF) as compared to heart failure patients with reduced left ventricular ejection fraction.We sought to explore the diagnostic value of serum levels of soluble ST2 (sST2) combined with interleukin-33 (IL-33) for the diagnosis of HF-pEF in this study. Methods: A total of 376 patients with HF-pEF (HF group), 376 matched-control patients without heart failure who shared similar clinical characteristics (non-HF group) were included in the study.Another 500 healthy individuals were recruited for assessing the normal ranges of IL-33 and sST2.Serum levels of NT-proBNP were measured by chemi-luminescence assay, while IL-33 and sST2 were measured by enzyme linked immunosorbent assay. Results: Serum levels of IL-33 and sST2 were not normally distributed in healthy population.Serum concentrations of IL-33 and sST2 were significantly higher in HF-pEF patients than in patients in non-HF group (median, IL-33: 0.437 µg/L vs. 0.127 µg/L, P<0.01; sST: 0.118 µg/L vs. 0.067 µg/L, P<0.01). The area under receiver operating characteristic curve (AUC) of sST2 for detecting HF-pEF was 0.763 (95%CI 0.729-0.795, P<0.01), with 71.01% sensitivity and 66.75% specificity, the AUC was 0.884 (95%CI 0.859-0.908, P<0.01), with 80.05% sensitivity and 81.91% specificity in patients with serum IL-33 higher than 0.117 µg/L (median level of serum IL-33 in healthy individuals, n=306). The AUC of NT-proBNP for detecting HF-pEF was 0.83, with 74.73% sensitivity and 84.57% specificity.The AUC of sST2 for detecting HF-pEF was significantly higher than NT-proBNP in population with high serum IL-33 (AUC: 0.88 vs. 0.83, P<0.01). Conclusion: Serum sST2 could serve as a satisfactory biomarker for HF-pEF diagnosis, especially for patients with high serum IL-33 concentrations.

[Comparison on metabolic disorders and uric acid levels between patients with primary aldosteronism and essential hypertension].

Objective: To compare the incidence of metabolic disorders and uric acid (UA) levels between patients with primary aldosteronism (PA) and essential hypertension (EH), and to explore factors associated with UA levels in these patients. Methods: A total of 117 PA and 117 EH patients individually matched by sex, age, blood pressure and duration of hypertension were recruited from in-hospital patients who were hospitalized in our department because of suspicion of secondary hypertension from January 2008 to December 2014. Clinical data including metabolic disorders and UA levels were analyzed. Results: (1) Body mass index (BMI), waist circumference, plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA) were significantly higher in EH than in PA group (all P<0.05). Prevalence of diabetes mellitus or impaired glucose tolerance (DM+ IGT) was significantly higher in EH than in PA group (41.9% (49/117) vs. 17.1% (20/117), P<0.01). The prevalence of metabolic syndrome (MS) was also significantly higher in EH than in PA group (51.3% (60/117) vs. 24.8% (29/117), P<0.01). (2) EH patients had higher homeostasis model assessment for insulin resistance (HOMA-IR) and lower insulin sensitivity index composite (ISI comp) than PA patients, but basic insulin secretion index (HOMA-ß) and modified ß cell function index (MBCI) were significantly lower in PA than in EH group (P<0.05). (3) With regard to target organs damages, PA patients revealed higher 24-hour urinary protein, urinary albumin excretion rate (UAER), urinary IgG, urinary α-1 microglobulin, left ventricular mass index and lower urine specific gravity than EH patients (all P<0.05). There was no significant difference in estimated glomerular filtration rate (eGFR) between two groups (P=0.103). (4) UA level was significantly lower in PA group than in EH group ((314.00±89.52) µmol/L vs. (379.16±101.25) µmol/L, P<0.01). Higher plasma aldosterone concentration and lower plasma renin activity were associated with lower UA level in PA group. Conclusions: Compared with sex, age and hypertension duration matched EH patients, PA patients revealed lower UA level and less severe abnormalities of glucose and lipid metabolism, but are associated with severer renal and cardiac damages. The reduced UA level in PA patients is possibly due to the high plasma aldosterone concentration and low plasma renin activity.

[Impact of novel P2Y12 receptor inhibitors on platelet reactivity in acute coronary syndrome patients undergoing percutaneous coronary intervention].

OBJECTIVE: To investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients. METHODS: Between October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU<208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again. RESULTS: There were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P<0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P<0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P<0.05). CONCLUSION: Novel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.

CD8α¯ DC is the major DC subset which mediates inhibition of allergic responses by Schistosoma infection.

Our and others' previous studies have shown that Schistosoma japonicum (SJ) infection can inhibit allergic reactions. We recently reported that DCs played an important role in SJ infection-mediated inhibition of allergy, which was associated with enhanced IL-10 and T regulatory cell responses. Here, we further compared the role of CD8α(+) DC and CD8α(-) DC subsets for the inhibitory effect. We sorted CD8α(+) DC (SJCD8α(+) DC) and CD8α(-) DC (SJCD8α(-) DC) from SJ-infected mice and tested their ability to modulate allergic responses in vivo. The data showed that the adoptive transfer of SJCD8α(-) DC was much more efficient than SJCD8α(+) DC for the suppression of allergic airway eosinophilia, mucus overproduction, antigen-specific IgE responses, and Th2 cytokines (IL-4 and IL-5). More importantly, we found that the transfer of SJCD8α(-) DC, but not SJCD8α(+) DC, significantly increased IL-10 and TGF-ß production following OVA exposure. As control, the transfer of DC subsets from naïve mice had no significant effect on allergic inflammation. In addition, SJCD8α-DC expressed significantly higher IL-10 but lower IL-12, CD80 and CD86 than SJCD8α(+) DC, fitting a tolerogenic phenotype. The results suggest that CD8α(-) DC is the predominant DC subset which is involved in the parasitic infection-mediated inhibition of allergic inflammation and possibly through enhancing immunomodulatory cytokine (IL-10 and TGF-ß) production.

Adoptive transfer of dendritic cells isolated from helminth-infected mice enhanced T regulatory cell responses in airway allergic inflammation.

Our and others' previous studies have shown that Schistosoma japonicum (SJ) infection can inhibit allergic reactions. Moreover, we found that adoptive transfer of dendritic cells (DCs) from inhibited mice showed a similar inhibitory effect on allergy, suggesting a critical role of DCs in SJ-infected mediated inhibition of allergy. In this study, we further examined the mechanism by which DCs contribute to inhibition of allergy. Our results showed that DCs from SJ-infected mice (SJDCs) produced significantly higher levels of IL-10 compared to those from naive control mice (NDCs). Adoptive transfer of SJDCs, unlike NDCs, significantly increased CD4+CD25+Foxp3+ T cells and CD4+CD25+IL-10+ T cells regulatory T-cell responses in vivo. This was correlated with significantly reduced production of IL-4 and IL-5 by CD4+ T cells, eotaxin in lung tissues and reduced airway allergic inflammation in the SJDC recipients following allergen sensitization and challenge. These data suggest that helminth infection may induce tolerogenic DCs that can inhibit the development of airway allergic inflammation through enhancing T regulatory cell responses.

[Effect of mm-LDL on NF-kB activation in endothelial cell].

OBJECTIVE: To investigate the signal transduction pathway of NF-kB activated by minimally modified low density lipoprotein (mm-LDL) in endothelial cells and the effect of NF-kB on platelet derived growth factor b (PDGFb) mRNA expression. METHODS: mm-LDL was prepared through iron oxidation by dialyzing the native LDL against FeSO4 in PBS. Endothelial cells were incubated in a medium containing mm-LDL, TNF, and IL-1 respectively and electrophoretic mobility shift assay (EMSA) was displayed to check on the activation of NF-kB. Luciferase reporter gene was analysed to investigate the effect of nuclear factor inducing kinase (NIK), inhibitor of NF-kB kinase alpha (IKK alpha) and inhibitor of NF-kB kinase beta (IKK beta) on NF-kB activation. In addition, endothelial cells were transfected using PDGFb promoter-luciferase for reporter gene analysis or transfected with mut-NIK for slot blot analysis to study the effect of NF-kB on PDGFb mRNA expression. RESULTS: mm-LDL was able to activate NF-kB in endothelial cells. mut-NIK and mut-IKK beta inhibited luciferase activity induced by mm-LDL. mm-LDL could also enhance luciferase activity controlled by upstream sequence of PDGFb promoter which contains element interacting with NF-kB. Result of slot blot showed inhibition of PDGFb mRNA expression by mut-NIK in the endothelial cells stimulated by mm-LDL. CONCLUSION: mm-LDL may activate NF-kB through NIK-IKK beta pathway and promote PDGFb mRNA expression in endothelial cells.

Effects of Panax notoginseng saponin Rg1 on cardiac electrophysiological properties and ventricular fibrillation threshold in dogs.

AIM: To study the effects of Rg1 isolated from saponins of Panax notoginseng on cardiac electrophysiological properties and ventricular fibrillation threshold (VFT). METHODS: Seventeen open-chest dogs were randomly allocated into a Rg1 group (20 mg kg-1, iv) and a control group. The electrophysiological variables and VFT were evaluated by standard electric stimuli and monophasic action potential (MAP) recording. RESULTS: Rg1 prolonged sinus node recovery time (SNRT) by 19.1%, AV conduction Wenckebach cycle length (AVWCL) by 7.1%, and ventricular effective refractory period (VERP) by 7.9%. It prolonged ventricular MAPD30, MAPD50, and MAPD90 by 25.5%, 24.2%, and 13.5%, respectively. VFT was increased by 19.2%. CONCLUSION: Rg1 prolonged ventricular refractoriness and repolarization, and increased VFT. It was indicated that cardiac electrophysiological effects of Rg1 were similar to those of amiodarone.

Anticipatory saccades in smooth pursuit: task effects and pursuit vector after saccades.

The dramatic improvement in smooth pursuit performance seen while analyzing the pursuit target has been ascribed to attention enhancement. With a periodic constant velocity target trajectory we ran a concurrent listening condition instead, to see if this mild distraction would degrade performance. Performance improved somewhat with the listening task, suggesting that displacing attentional effort from pursuit accuracy, rather than increasing it, brings better pursuit performance. Catch-up saccades were evenly distributed across tracking, listening, and target analysis conditions, but anticipatory and overshooting saccades were almost eliminated with target analysis. Thus the poor pursuit seems to have been caused by anticipatory and overshooting saccades, produced erroneously in the attempt to perform purposive smooth pursuit. Pursuit velocity immediately following anticipatory saccades was reduced such that the target would catch up with the point of gaze when it reached the endpoint of its trajectory, indicating a predictive goal other than instantaneous target foveation and velocity match.

Comparison of cardiac electrophysiologic effects of experimental hypothyroidism and chronic oral amiodarone administration in dogs.

A comparative study on ventricular electrophysiologic effects of experimental hypothyroidism and chronic oral amiodarone administration was made in canine models, with the application of electrical stimulation and monophasic action potential recording. The results showed similar effects possessed by hypothyroidism and amiodarone, which included prolongations in ventricular repolarization and refractoriness, an increase in ventricular fibrillation threshold, and a decrease in the incidence of reperfusion ventricular fibrillation. The differences were that hypothyroidism primarily lengthened phase 2 repolarization and had no effects on intraventricular conduction time, whereas amiodarone lengthened both phase 2 and phase 3 repolarization and suppressed myocardial conduction velocity.