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22 10月 2019

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Author : 伤口世界

对各类型急慢性创面如烧伤、褥疮、下肢血管性溃疡、糖尿病足溃疡、慢性骨髓炎、手术后创面不愈、放射性溃疡等疾病的诊断和治疗方面有一定临床经验，擅长慢性骨髓炎的诊疗。医学硕士，毕业于上海交通大学医学院骨科学硕士，现任上海交通大学医学院附属第九人民医院创面修复科住院医师，主要从事九院创面修复科的临床工作。

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Correlation between myocardial work and disease activity in rheumatoid arthritis patients with preserved left ventricular ejection fraction: a retrospective study based on non‑invasive pressure‑strain loop 2025-08-06 00:00

Xiaolong Yu1 · Jing Xi1 · Jiabiao Wu2 · Ruixiao Song1

Received: 24 November 2024 / Revised: 18 January 2025 / Accepted: 16 February 2025 / Published online: 5 March 2025

© The Author(s) 2025

* Ruixiao Song 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

1 Department of Ultrasonics, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China

2 Rheumatology and Immunology Department, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China

Abstract

Background Early cardiac damage is very common in RA patients, but it is usually subclinical. Therefore, finding a non invasive method for the early detection and treatment of cardiac damage in autoimmune diseases is particularly important.

Objective To evaluate left ventricular function changes in rheumatoid arthritis (RA) patients with preserved left ventricular ejection fraction (LVEF) using left ventricular pressure-strain loop (LV-PSL) technology and to explore the correlation between myocardial work (MW) and disease activity.

Methods A total of 62 RA patients with preserved LVEF, treated at Wujin Hospital Affiliated with Jiangsu University from January 2021 to September 2023, were included. Patients were categorized into low (25), medium (18), and high (19) disease activity groups based on the 28 joint disease activity score (DAS28). A control group of 29 healthy individuals was also established. LV-PSL technology assessed left ventricular global longitudinal strain (GLS) and MW parameters: global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE). Cor relations between MW parameters, GLS, LVEF, and DAS28 scores were analyzed.

Results There were no significant differences in general data between study and control groups (p>0.05). However, labora tory indicators (RF, CRP, ESR) showed significant differences (p<0.05). GWI, GCW, GWE, and GLS were significantly lower in the high disease activity group compared to controls (p<0.05). GWI, GCW, and GWE were positively correlated with LVEF and absolute GLS, while GWW correlated negatively with LVEF (p<0.05).

Conclusion RA disease activity is closely associated with impaired myocardial work. LV-PSL technology effectively moni tors myocardial function abnormalities in RA patients, providing valuable insights for clinical management.

Key PointsMyocardial work is significantly impaired in RA patients with high disease activity. Left ventricular pressure-strain loop (LV-PSL) technology effectively assesses cardiac function in this patient population. Increased disease activity correlates with reduced myocardial work parameters.

Keywords Left ventricular pressure-strain loop · Myocardial work · Rheumatoid arthritis · Speckle-tracking echocardiography
Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo E−/−/LDLR−/− Double‑Knockout Mice 2025-08-05 00:00

Ewelina Czuba‑Pakuła1 · Jolanta Ochocińska2 · Sebastian Głowiński3 · Alicja Braczko4 · Ryszard T. Smoleński4 · Grażyna Lietzau1 · Przemysław Kowiański1,3

Received: 14 August 2024 / Accepted: 7 May 2025 © The Author(s) 2025

* Ewelina Czuba-Pakuła 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

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1 Division of Anatomy and Neurobiology, Faculty of Medicine, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland

2 Department of Conservative Dentistry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland

3 Institute of Health Sciences, Pomeranian University in Słupsk, Słupsk, Poland

4 Department of Biochemistry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland

Abstract

Hypercholesterolemia (Hch) is a risk factor for cerebrovascular and neurodegenerative diseases, manifesting with symptoms that vary depending on damage to specific brain regions. Hch triggers inflammatory responses and cell death. However, the progression of these processes in relation to the duration of Hch and the location of pathology in the central nervous system remains unclear. Therefore, we aimed to investigate (1) the impact of age and duration of Hch on neuroinflammatory responses and programmed cell death in the brain and (2) the intensity of these processes in various brain areas during Hch. In this study, we used 3-, 6-, and 12-month-old male Apo E−/−/LDLR−/− double-knockout mice and age-matched wild-type C57BL/6 mice (control group). Concentrations of cytokines IL-1β, IL-4, and IL-6, as well as apoptotic mediators AIF and Cas-3, were measured using enzyme-linked immunosorbent assay in the whole brain and separately in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR). The results showed that the Hch-induced release of cytokines IL-1β and IL-6, decreased expression of IL-4, and elevated level of apoptotic markers AIF and Cas-3 correlated with Hch duration. The inflammatory response and expression of apoptotic markers were more pronounced in the HIP and STR compared to the PFCx. Our results indicate a correlation between the neurodegenerative effects of Hch and its duration and highlight the varying susceptibility of different brain areas to Hch-induced damage.

Graphical Abstract

Hypercholesterolemia (Hch)-induced inflammatory response and programmed cell death activation in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR) of 3-, 6-, and 12-month-old, Apo E−/−/LDLR−/− double-knockout mice. In three age-groups the Hch-induced response involved release of inflammatory cytokines (IL-1ß and IL-6), a decrease of anti-inflammatory (IL-4) cytokine level, and activation of programmed cell death markers (AIF and Cas-3). The inflam matory response and expression of apoptotic markers were more pronounced in the HIP and STR, compared to the PFCx.

Keywords Apoptosis · Atherosclerosis · Cytokines · Hypercholesterolemia · Neurodegeneration · Neuroinflammation
Salt‑sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity 2025-08-04 00:00

S.Verouti1,2,3 · G. Aeschlimann1 · Q. Wang4 · D. Ancin Del Olmo1 · A. C. Peyter5 · S. Menétrey5 ·D.V. Winter6 · A. Odermatt6 · D. Pearce7 · E. Hummler1,2 · P. E. Vanderriele1,2

Received: 30 April 2024 / Revised: 22 August 2024 / Accepted: 23 August 2024 / Published online: 10 September 2024 © The Author(s) 2024

* P. E. Vanderriele 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

1 Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland

2 National Center of Competence in Research, Kidney.CH, Lausanne, Switzerland

3 Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland

4 Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland

5 Neonatal Research Laboratory, Clinic of Neonatology, Department Woman-Mother-Child, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland

6 Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

7 Department of Medicine and Cellular & Molecular Pharmacology, University of California, San Francisco, USA

Abstract

In humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/− rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active poly unsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregu lated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.

Keywords Adrenal gland hyperplasia · Hypertension · Glucocorticoid receptor · Soluble epoxide hydrolase · Chrousos syndrome

Abbreviations

ACTH Adrenocorticotropic hormone DiHETrE Dihydroxyeicosatrienoic acid DiHOME Dihydroxy-9Z-octadecenoic acid EET Epoxyeicosatrienoic acid EpETrE Epoxyeicosatrienoic acid GR Glucocorticoid receptor HETE Hydroxyeicosatetraenoic acid KODE Ketooctadecenoic acid sEH Soluble epoxide hydrolase

◂Fig.1 GR+/em4 rats presented adrenal hyperplasia of the cortex and the medulla accompanied by a trend toward an increase in the plasma glucocorticoid concentration under standard diet. A Scheme of the wild-type (GR+, upper panel) and the mutated GRem2 (middle) and GRem4 (lower panel) structure of the GR. B Representation of the zinc finger domain of the GR with the deleted amino acids in red. C Rep resentative macroscopic images (scale bar, 1 mm) and D hematoxy lin/eosin-stained sections of whole adrenal glands (left panels; scale bar, 1 mm) and cortex (right panels; scale bar, 300 µm) from 3- to 4-week-old male GR+/+ and GR+/em4 rats (n=3) fed a standard salt diet; zf, zona fasciculata; zg, zona glomerulosa. E Measurement of the adrenal weight/body weight ratio (GR+/+, n=12; GR+/em4, n=14) and F cortex (left) and medulla (right panel) size (GR+/+ (n=3) and GR+/em4 (n=4)). G Determination of plasma concentrations of the glucocorticoids corticosterone, 11-dehydrocorticosterone and the corticosterone/11-dehydrocorticosterone ratio and H the mineralo corticoid aldosterone and its precursor 11-deoxycorticosterone in the morning (7–8 am) and afternoon (6–7 pm) of GR+/+ and GR.+/em4 (n=4 – 16) rats. The size measurements were evaluated using QuPath (vO.4.4), and the plasma concentrations were evaluated by two-way ANOVA and subsequently compared with an unpaired two tailed t test with Welch’s correction. The values are presented as the mean±SEMs. Differences were assessed at *P<0.05 and **P<0.01

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主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

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主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

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