Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is ...not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.
Estimated pulse wave velocity (ePWV) has been proposed as a potential approach to estimate carotid-femoral pulse wave velocity. However, the potential of ePWV in predicting all-cause mortality (ACM) ...and cardiovascular disease mortality (CVM) in the general population is unclear.
We conducted a prospective cohort study using the data of 33,930 adults (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 until the end of December 2019. The study outcomes included ACM and CVM. Survey-weighted Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between ePWV and ACM and CVM. To further investigate whether ePWV was superior to traditional risk factors in predicting ACM and CVM, comparisons between ePWV and the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) models were performed. Integrated Discriminant Improvement (IDI) and Net Reclassification Improvement (NRI) were employed to analyze differences in predictive ability between models.
The weighted mean age of the 33,930 adults included was 45.2 years, and 50.28% of all participants were men. In the fully adjusted Cox regression model, each 1 m/s increase in ePWV was associated with 50% and 49% increases in the risk of ACM (HR 1.50; 95% CI, 1.45-1.54) and CVM (HR 1.49; 95% CI, 1.41-1.57), respectively. After adjusting for FRS, each 1 m/s increase in ePWV was still associated with 29% (HR 1.29; 95% CI, 1.24-1.34) and 34% (HR 1.34; 95% CI, 1.23-1.45) increases in the risk of ACM and CVM, respectively. The area under the curve (AUC) predicted by ePWV for 10-year ACM and CVM were 0.822 and 0.835, respectively. Compared with the FRS model, the ePWV model improved the predictive value of ACM and CVM by 5.1% and 3.8%, respectively, with no further improvement in event classification. In comparison with the PCE model, the ePWV model's ability to predict 10-year ACM and CVM was improved by 5.1% and 3.5%, and event classification improvement was improved by 34.5% and 37.4%.
In the U.S. adults, ePWV is an independent risk factor for ACM and CVM and is independent of traditional risk factors. In the general population aged 20 to 85 years, ePWV has a robust predictive value for the risk of ACM and CVM, superior to the FRS and PCE models. The predictive power of ePWV likely originates from the traditional risk factors incorporated into its calculation, rather than from an indirect association with measured pulse wave velocity.
The combination of surface densification and superheated steam treatment is an effective method to improve the mechanical properties and dimensional stability of low-density wood. The objective of ...the current work is to evaluate the effects of superheated steam treatment on the micromechanical behavior of surface densified wood. The microstructure, chemical composition, cellulose crystalline structure, and micromechanical behavior of surface densified wood under different superheated steam pressures were investigated. Results indicated that both 0.1 MPa and 0.3 MPa superheated steam treatments increased the elastic modulus and hardness of fiber cell walls in surface densified wood. However, the average creep ratio and maximum creep compliance J(50) of surface densified wood under 0.3 MPa decreased by 41.59% and 6.76%, respectively, compared with untreated wood. The improvement of elastic modulus, hardness and creep resistance of surface densified wood treated with superheated steam was associated with the increase of relative crystallinity (CrI) and crystalline size. In addition, 0.3 MPa superheated steam treatment displayed a better effect on the enhancement of the elastic modulus, hardness, and creep resistance of the fiber cell wall than 0.1 MPa superheated steam treatment.
Summary
Objective
Saline infusion test (SIT), captopril challenge test (CCT), fludrocortisone suppression test (FST) and oral sodium loading test (SLT) are recommended by the Endocrine Society's ...Clinical Practice Guidelines to diagnose primary aldosteronism, but which one is the best remains controversial. We aimed to summarize the available comparative data and evaluate the diagnostic accuracy of these four tests.
Design
We searched PubMed, Embase and the Cochrane Library for relevant studies published between January 1980 and January 2018.
Patients
Eligible studies reported on the accuracy of one or more of the four confirmatory tests in patients suspected of PA.
Measurements
Two reviewers independently conducted the data extraction of all selected studies, which consisted of study characteristics and data to estimate the summary receiver operating characteristic (SROC) curve and the corresponding summary area under the curve (SAUC), pooled sensitivity and specificity, diagnostic odds ratios (DOR) with 95% confidence interval (CI).
Results
We identified 26 articles including 3686 patients. Fifteen articles evaluated the diagnostic accuracy of CCT, 10 of SIT, 1 of FST and none of SLT. For CCT, the SAUC was 0.9207, and the pooled sensitivity and specificity were 0.87 (95% CI: 0.84‐0.89) and 0.84 (95% CI: 0.81‐0.86), respectively. For SIT, the SAUC was 0.9232, and the pooled sensitivity and specificity were 0.85 (95% CI: 0.82‐0.87) and 0.87 (95% CI: 0.85‐0.89), respectively. For FST, the pooled sensitivity and specificity were 0.87 (95% CI: 0.66‐0.97) and 0.95 (95% CI: 0.82‐0.99), respectively. Overall, we found no significant differences in the diagnostic accuracy of CCT and SIT.
Conclusions
CCT and SIT exhibit high and comparable accuracy for diagnosing PA. CCT may be a more feasible alternative as it is safe and much easier to perform.
Abstract
Context
The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma ...aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited.
Objective
To develop and validate optimized criteria for sparing CFT in the diagnosis of PA.
Design and Setting
The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort.
Participants
Hypertensive patients who completed PA screening and CFT.
Main Outcome Measure
Diagnostic value of the optimized criteria.
Results
In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 μIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02).
Conclusions
Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.
Dyslipidemia frequently coexists with hypertension in the population. Apolipoprotein B (ApoB) is increasingly considered a more potent predictor of cardiovascular disease (CVD). Abnormal levels of ...serum ApoB can potentially impact the mortality risk.
The prospective cohort study employed data from the National Health and Nutrition Examination Survey (NHANES), which was performed between 2005 and 2016, with follow-ups extended until December 2019. Serum ApoB concentrations were quantified using nephelometry. In line with the NHANES descriptions and recommendations, the reference ranges for ApoB concentrations are 55-140 and 55-125 mg/dL for men and women, respectively. Participants were categorized into low, normal, and high ApoB levels. The low and high groups were combined into the abnormal group. In this study, all-cause mortality (ACM) and CVD mortality (CVM) were the endpoints. Survey-weighted cox hazards models were used for evaluating the correlation between serum ApoB levels and ACM and CVM. A generalized additive model (GAM) was employed to examine the dose-dependent relationship between ApoB levels and mortality risk.
After a median of 95 (interquartile range: 62-135) months of follow-up, 986 all-cause and 286 CVD deaths were recorded. The abnormal ApoB group exhibited a trend toward an elevated risk of ACM in relative to the normal group (HR 1.22, 95% CI: 0.96-1.53). The risk of CVM was elevated by 76% in the ApoB abnormal group (HR 1.76, 95% CI: 1.28-2.42). According to the GAM, there existed a nonlinear association between serum ApoB levels and ACM (P = 0.005) and CVM (P = 0.009).
In the US hypertensive population, serum Apo B levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. Importantly, abnormal Apo B levels were related to an elevated risk of ACM and CVM. These risks were especially high at lower Apo B levels. The obtained findings emphasize the importance of maintaining appropriate Apo B levels to prevent adverse outcomes in hypertensive individuals.
Abstract
Context
More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy.
Objective
The objective of this ...work is to develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA.
Design and Setting
The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort.
Participants
Participants comprised patients with UPA achieving complete biochemical success after unilateral adrenalectomy.
Main Outcome Measure
Measurements included the predictive performance of the NBPS compared with 2 previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score.
Results
Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone-to-renin ratio, and target organ damage. The nomogram showed good C indices and calibration curves both in Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of the NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to the ARS (0.745 0.667-0.812, P = .019) and PASO score (0.747 0.670-0.815, P = .012). The AUC of the NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than the ARS (0.745 95% CI, 0.672-0.810, P = .045), but not significantly different from the PASO score (0.825 95% CI, 0.758-0.880, P = .911).
Conclusion
The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.
Background
Significant evidence suggests that asthma might originate from low-grade systemic inflammation. Previous studies have established a positive association between the systemic ...immune-inflammation index (SII) and the systemic inflammation response index (SIRI) levels and the risk of stroke. However, it remains unclear whether SII, SIRI and the prevalence of stroke are related in individuals with asthma.
Methods
The present cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. SII was calculated using the following formula: (platelet count
×
neutrophil count)
/
lymphocyte count. SIRI was calculated using the following formula: (neutrophil count × monocyte count)/lymphocyte count. The Spearman rank correlation coefficient was used to determine any correlation between SII, SIRI, and the baseline characteristics. Survey-weighted logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to determine the association between SII, SIRI, and stroke prevalence. The predictive value of SII and SIRI for stroke prevalence was assessed through receiver operating characteristic (ROC) curve analysis, with the area under the ROC curve (AUC) being indicative of its predictive value. Additionally, clinical models including SIRI, coronary heart disease, hypertension, age, and poverty income ratio were constructed to evaluate their clinical applicability.
Results
Between 1999 and 2018, 5,907 NHANES participants with asthma were identified, of which 199 participants experienced a stroke, while the remaining 5,708 participants had not. Spearman rank correlation analysis indicated that neither SII nor SIRI levels exhibited any significant correlation with the baseline characteristics of the participants (r<0.1). ROC curves were used to determine the optimal cut-off values for SII and SIRI levels to classify participants into low- and high-level groups. Higher SII and SIRI levels were associated with a higher prevalence of stroke, with ORs of 1.80 (95% CI, 1.18-2.76) and 2.23 (95% CI, 1.39-3.57), respectively. The predictive value of SIRI (AUC=0.618) for stroke prevalence was superior to that of SII (AUC=0.552). Furthermore, the clinical model demonstrated good predictive value (AUC=0.825), with a sensitivity of 67.1% and specificity of 87.7%.
Conclusion
In asthmatics, higher levels of SII and SIRI significantly increased the prevalence of stroke, with its association being more pronounced in individuals with coexisting obesity and hyperlipidaemia. SII and SIRI are relatively stable novel inflammatory markers in the asthmatic population, with SIRI having a better predictive value for stroke prevalence than SII.
TiO2 films exhibiting structural colors were successfully prepared using one-step electrochemical oxidation. Results of theoretical analyses and digital simulations revealed that the structural color ...of a TiO2 thin film could be regulated by adjusting oxidation voltage and oxidation time with different oxidation voltages leading to changes in structural color annulus number. At a low oxidation voltage, each thin film exhibited a single structural color, while thin films with different structural colors were obtained by varying the oxidation time. By contrast, at a higher oxidation voltage, each film exhibited iridescent and circular structural color patterns associated with symmetrical decreases in surface oxidation current density along radial lines emanating from the film center to its outer edges. TiO2 films exhibiting iridescent structural colorations have broad application prospects in industrial fields related to photocatalysis and photovoltaic cells.
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