Abstract
Aim
Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and ...healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease.
Methods
Whole‐genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network‐based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real‐time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves.
Results
We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (
HLA
)
class I
,
ADAR
, and
OAS2
was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS.
Conclusion
Clinical sample validation suggested that
HLA class I
,
ADAR
, and
OAS2
might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.
Background:
Primary aldosteronism (PA) has been associated with atherosclerosis beyond the extent of essential hypertension, but the impact of albuminuria remains unknown.
Objective:
To investigate ...the effect of concomitant albuminuria on arterial stiffness in PA.
Design:
Prospective cohort study.
Methods:
A prospective cohort study was conducted to evaluate the association of albuminuria (>30 mg/g in morning spot urine) with arterial stiffness, as measured non-invasively by pulse wave velocity (PWV) in patients with PA. Propensity score matching (PSM) with age, sex, diabetes, systolic and diastolic blood pressure, creatinine, potassium, number of antihypertensive medications, and hypertension history was used to balance baseline characteristics. The effects of albuminuria on PWV before and 1 year after treatment were analyzed.
Results:
A total of 840 patients with PA were enrolled, of whom 243 had concomitant albuminuria. After PSM, there were no significant differences in baseline demographic parameters except alpha-blocker and spironolactone use. PWV was greater in the presence of albuminuria (p = 0.012) and positively correlated with urine albumin–creatinine ratio. Multivariable regression analysis identified albuminuria, age, body weight, systolic blood pressure, and calcium channel blocker use as independent predictors of PWV. As for treatment response, only PA patients with albuminuria showed significant improvements in PWV after PSM (p = 0.001). The magnitude of improvement in PWV increased with urine albumin–creatinine ratio and reached plateau when it exceeded 100 mg/g according to restricted cubic spline analysis.
Conclusion:
Concomitant albuminuria in PA was associated with greater arterial stiffness and more substantial improvement after targeted treatment. Both the baseline and the improved extent of PWV increased in correlation with rising urine albumin–creatinine ratio levels, reaching a plateau when the urine albumin–creatinine ratio surpassed 100 mg/g.
Plain language summary
Albuminuria and primary aldosteronism synergistically induce atherosclerosis
Albuminuria is a common comorbidity in patients with primary aldosteronism (PA), and both has been established to potentiate atherosclerosis. However, the interaction in between remained enigmatic. In this study, we accessed the synergistic vascular impact in a prospectively enrolled cohort. Arterial rigidity was assessed non-invasively by brachial–ankle pulse wave velocity. Concomitant albuminuria in patients with PA was associated with pronouncedly greater arterial stiffness and was further demonstrated as an independent predictor for atherosclerosis. In addition, PA-targeted treatment effectively reversed arterial stiffness, especially in individuals with concomitant albuminuria. The beneficial effect of PA-targeted treatment on PWV increased with rising urine albumin–creatinine ratio levels, eventually plateauing when the UACR surpassed 100 mg/g.
Hyperaldosteronism has adverse effects on cardiovascular structure and function. Laparoscopic adrenalectomy is the gold standard for patients with unilateral primary aldosteronism. For unilateral ...primary aldosteronism patients unable or unwilling to undergo surgery, the effects of mineralocorticoid receptor antagonists (MRAs) on the reversibility of arterial stiffness and other clinical data remain unclear. We aimed to compare the reversibility of arterial stiffness using pulse wave velocity (PWV) and other clinical parameters between surgically and medically treated unilateral primary aldosteronism patients.
We prospectively enrolled 306 unilateral primary aldosteronism patients, of whom 247 received adrenalectomy and 59 received medical treatment with MRAs. Detailed medical history, basic biochemistry and PWV data were collected in both groups before treatment and 1 year after treatment. After propensity score matching (PSM) for age, sex, SBP and DBPs, 149 patients receiving adrenalectomy and 54 patients receiving MRAs were included for further analysis.
After PSM, the patients receiving adrenalectomy had a greater reduction in blood pressure, increase in serum potassium, and change in PWV (ΔPWV, -53 ± 113 vs. -10 ± 140 cm/s, P = 0.028) than those receiving MRAs 1 year after treatment. Multivariable regression analysis further identified that surgery (compared with MRA treatment), baseline PWV, baseline DBP, the change in DBP and the use of diuretics were independently correlated with ΔPWV.
Adrenalectomy is superior to MRA treatment with regards to vascular remodeling when treating unilateral primary aldosteronism patients.
This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ...ultrasonographic elastography(UE).
From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.
The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4.
Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The ...Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.
This research presents the optimization and proposal of P- and N-type 3-stacked Si
Ge
/Si strained super-lattice FinFETs (SL FinFET) using Low-Pressure Chemical Vapor Deposition (LPCVD) epitaxy. ...Three device structures, Si FinFET, Si
Ge
FinFET, and Si
Ge
/Si SL FinFET, were comprehensively compared with HfO
= 4 nm/TiN = 80 nm. The strained effect was analyzed using Raman spectrum and X-ray diffraction reciprocal space mapping (RSM). The results show that Si
Ge
/Si SL FinFET exhibited the lowest average subthreshold slope (SS
) of 88 mV/dec, the highest maximum transconductance (G
) of 375.2 μS/μm, and the highest ON-OFF current ratio (I
/I
), approximately 10
at V
= 0.5 V due to the strained effect. Furthermore, with the super-lattice FinFETs as complementary metal-oxide-semiconductor (CMOS) inverters, a maximum gain of 91
was achieved by varying the supply voltage from 0.6 V to 1.2 V. The simulation of a Si
Ge
/Si super-lattice FinFET with the state of the art was also investigated. The proposed Si
Ge
/Si strained SL FinFET is fully compatible with the CMOS technology platform, showing promising flexibility for extending CMOS scaling.
Background:
Aldosterone excess in primary aldosteronism (PA) has been linked to insulin resistance, and diabetes mellitus has been associated with increased arterial stiffness and worse ...cardiovascular outcomes. However, the impact of diabetes on baseline and post-treatment arterial stiffness in patients with PA is unknown.
Methods:
This study prospectively enrolled 1071 PA patients, of whom 177 had diabetes and 894 did not. Clinical, biochemical, and brachial-ankle pulse wave velocity (baPWV) data were analyzed at baseline and 1 year after PA-specific treatment. After propensity score matching of age, sex, body mass index, systolic and diastolic blood pressure, hypertension duration, and number of antihypertensive medications, 144 patients with diabetes and 320 without diabetes were included for further analysis.
Results:
After propensity score matching, the baseline characteristics were balanced between the diabetes and nondiabetes groups except for fasting glucose, HbA1c, and lipid profiles. The patients with diabetes had significantly worse baseline baPWV compared with those without diabetes. After multivariable linear regression, the presence of diabetes mellitus remained a significant predictor of worse baseline mean baPWV (β: 46.3, 95% confidence interval: 2.9–89.7, p = 0.037). After 1 year of PA-specific treatment, only the nondiabetes group had significant recovery of mean baPWV (1661.8 ± 332.3 to 1565.0 ± 329.2 cm/s, p < 0.001; Δ = −96.8 ± 254.6 cm/s). In contrast, the diabetes group had less improvement (1771.2 ± 353.8 cm/s to 1742.0 ± 377.2 cm/s, p = 0.259; Δ = −29.2 ± 263.2 cm/s) even though the systolic and diastolic blood pressure significantly improved in both groups.
Conclusion:
The presence of diabetes mellitus in PA patients was associated with worse baseline and less post-treatment recovery of arterial stiffness.
Primary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. ...Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which
somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of
somatic mutations on systemic organ damage.
PubMed literature research using keywords combination, including "aldosterone-producing adenoma," "somatic mutations," "
," "organ damage," "cardiovascular," "diastolic function," "metabolic syndrome," "autonomous cortisol secretion," etc.
APA patients with
somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of
somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery.
somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without
mutations.
Primary aldosteronism (PA) is a common cause of secondary hypertension and associated with higher incidence of new-onset atrial fibrillation (NOAF). However, the effects of surgical or medical ...therapies on preventing NOAF in PA patents remain unclear. The aim of this meta-analysis study was to assess the risk of NOAF among PA patients receiving mineralocorticoid receptor antagonist (MRA) treatment, PA patients receiving adrenalectomy, and patients with essential hypertension.
We performed the meta-analysis of the randomized or observational studies that investigated the incidence rate of NOAF in PA patients receiving MRA treatment versus PA patients receiving adrenalectomy from database inception until December 01, 2020 which were identified from PubMed, Embase, and Cochrane Library.
A total of 172 related studies were reviewed, of which three fulfilled the inclusion criteria, including a total of 2,705 PA patients. The results of meta-analysis demonstrated a higher incidence of NOAF among the PA patients receiving MRA treatment compared to the PA patients receiving adrenalectomy (pooled odds ratio OR: 2.83, 95% confidence interval CI: 1.76-4.57 in the random effects model,
= 0%). The pooled OR for the PA patients receiving MRA treatment compared to the patients with essential hypertension was 1.91 (95% CI: 1.11-3.28). The pooled OR for the PA patients receiving adrenalectomy compared to the patients with essential hypertension was 0.70 (95% CI: 0.28-1.79).
Compared to the essential hypertension patients and the PA patients receiving adrenalectomy, the patients with PA receiving MRA treatment had a higher risk of NOAF.
https://www.crd.york.ac.uk/prospero/, identifier CRD42021222022.
PDF
