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Sexual Dimorphism in Plantar Pressure Distribution Patterns. 足底压力分布模式的两性二态性。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
J Lorkowski, A Jóźwik, M Pokorski

Efficient management of foot disorders requires knowledge of plausible sexual dimorphic differences in the foot structure and function. Knowledge about foot dimorphism is yet unsettled. In the present study, we mapped the multizone plantar pressure distribution in a cohort of 298 healthy subjects of both sexes using the piezoelectric pedobarographic recordings. We investigated the hypothesis that sexual foot dimorphism would entail differences in plantar pressure distribution. We delved into the issue using the k-nearest neighbors' classifier (k-NN), a supervised machine learning algorithm, to predict the correct foot phenotype classification based on the plantar pressure and anthropometric and structural features. Based on the similarity measures, the classifier assigns unknown input data to the most common class, men or women, among the closest neighbors. The major finding was the unraveling of sex-specific foot dimorphism in healthy people. The k-NN was able to recognize the person's sex based on a few discriminatory features, with an outstandingly low misclassification rate. The pressure distribution on the plantar surface of the great toe, one of the orthopedic plantar surface zones, is the most distinct feature in differentiating the foot phenotype. The results also unraveled the presence of individuals whose foot features paradoxically corresponded with those classified for the opposite sex, i.e., the female foot was classified in the men's group and vice versa. In conclusion, the study supports the presence of sexual foot dimorphism. A pedobarographic examination supplemented with the k-NN algorithm for machine learning allows one to discriminate the foot sexual phenotype with high accuracy. The foot phenotype identities exist outside the gender binary. Insights into sexual foot dimorphism may streamline the management of foot disorders. Keywords Biomechanics " Foot " K-nearest neighbors' algorithm " Pedobarography " Plantar pressure " Foot dimorphism.

足部疾病的有效管理需要了解足部结构和功能中似是而非的两性二态差异。关于足部二态性的知识尚不明确。在本研究中,我们用压电式足底压仪记录了298名健康男女的足底压力分布。我们研究了两性足二态性会导致足底压力分布差异的假设。我们使用k近邻分类器(k-NN)(一种监督机器学习算法)深入研究了这个问题,该算法基于足底压力、人体测量和结构特征来预测正确的足部表型分类。基于相似性度量,分类器将未知输入数据分配给最近邻居中最常见的类,男性或女性。主要的发现是揭示了健康人的性别特异性足部二态性。k-NN能够基于一些歧视性特征来识别人的性别,错误分类率非常低。大脚趾是足底矫形区之一,其足底表面的压力分布是区分足型最明显的特征。研究结果还揭示了一些人的脚特征与被分类为异性的脚特征矛盾地对应,也就是说,女性的脚被分类为男性的脚,反之亦然。总之,该研究支持性足二态性的存在。足部检查与机器学习的k-NN算法相结合,可以高精度地区分足部性别表型。足部表型身份存在于性别二元之外。洞察性足二态可能简化足疾病的管理。生物力学;足部;k近邻算法;
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引用次数: 0
Predictive Value of Serum 25-Hydroxyvitamin D Levels in the Onset and Glycemic Control of Gestational Diabetes Mellitus. 血清25-羟基维生素D水平对妊娠期糖尿病发病及血糖控制的预测价值。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
Ling-Ling Zou, Wu Dai, Jun Ye, Yong-Hong Cao, Fa-Hui Lv

This study aimed to evaluate the predictive value of serum 25 hydroxyvitamin D (25(OH) D) levels in relation to the onset and glycemic control of gestational diabetes mellitus (GDM). This retrospective study analyzed clinical data of pregnant women who received routine prenatal care and were hospitalized at the Second People's Hospital of Hefei between January 2023 and January 2025. The study included 200 pregnant women diagnosed with GDM (study group) and 200 gestational age-matched pregnant women with normoglycemia (control group), selected through random sampling. Within the study group, 146 participants exhibited standard glycemic control (Y1 group), while 54 participants exhibited non-standard glycemic control (Y2 group) during hospitalization in the third trimester. Significant differences in serum 25(OH)D levels were observed between the control and study groups across all trimesters (53.82 ± 9.43), (56.73 ± 11.28), (49.65 ± 10.65) nmol/L, and (45.87 ± 8.45), (44.42 ± 10.04), (46.63 ± 9.87) nmol/L (p < 0.05). In the second trimester, serum 25(OH)D levels were negatively correlated with the oral glucose tolerance test (OGTT) values in the study group (p < 0.05). Comparison of the 25(OH)D levels in the third trimester between the Y1 group (48.95 ± 9.46) and the Y2 group (42.75 ± 10.23) nmol/L indicated that there was no significant statistical difference between the study group and the control group (49.65 ± 10.65 nmol/L) (p > 0.05). A receiver operating characteristic curve for first trimester 25(OH)D levels of pregnant women in the study group yielded an area under the curve of 0.84. Lower serum 25(OH)D levels were associated with an elevated risk of developing GDM and with poorer glycemic control in affected women. These findings indicate that first trimester serum 25(OH)D levels may serve as a valuable biomarker for the early prediction and management of GDM. Keywords Blood glucose " Correlation " Gestational diabetes mellitus " Pregnant women " 25-hydroxyvitamin D.

本研究旨在评价血清25(OH) D水平对妊娠期糖尿病(GDM)发病及血糖控制的预测价值。本研究回顾性分析了2023年1月至2025年1月在合肥市第二人民医院接受常规产前护理并住院的孕妇的临床资料。本研究随机抽取200名确诊为GDM的孕妇(研究组)和200名胎龄匹配且血糖正常的孕妇(对照组)。在研究组中,146例患者在妊娠晚期住院期间血糖控制标准(Y1组),54例患者在住院期间血糖控制不标准(Y2组)。对照组和研究组各妊娠期血清25(OH)D水平分别为(53.82±9.43)、(56.73±11.28)、(49.65±10.65)nmol/L和(45.87±8.45)、(44.42±10.04)、(46.63±9.87)nmol/L,差异均有统计学意义(p < 0.05)。在妊娠中期,研究组血清25(OH)D水平与口服葡萄糖耐量试验(OGTT)值呈负相关(p < 0.05)。Y1组妊娠晚期25(OH)D水平(48.95±9.46)与Y2组(42.75±10.23)nmol/L比较,实验组与对照组(49.65±10.65 nmol/L)差异无统计学意义(p < 0.05)。研究组孕妇妊娠早期25(OH)D水平的受试者工作特征曲线下面积为0.84。较低的血清25(OH)D水平与发生GDM的风险升高和较差的血糖控制有关。这些发现表明,妊娠早期血清25(OH)D水平可作为早期预测和管理GDM的有价值的生物标志物。血糖;相关性;妊娠期糖尿病;孕妇;
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引用次数: 0
Phase Angle in Bioelectrical Impedance: New Perspectives in Health and Body Composition Assessment. 生物电阻抗的相位角:健康和身体成分评估的新视角。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
J Jirků, J Křížová

The aim of this observational, descriptive, and cross-sectional study was to analyze the relationship between phase angle (PhA), determined by bioelectrical impedance analysis (BIA), and body composition parameters in healthy adult individuals. The study included 265 participants (122 women and 143 men) aged 18-77 years, examined at a nutritional outpatient clinic in Prague between April 2022 and December 2023. Segmental multi-frequency BIA was performed using the Tanita MC-780 MA analyzer with eight electrodes and frequencies of 5 kHz, 50 kHz, and 250 kHz. The mean PhA values were significantly higher in men than in women (6.29° vs. 5.57°; p < 0.001). A strong negative correlation between the extracellular water-to-total body water ratio (ECW/TBW) and PhA was observed in men (r = 0.78; p < 0.001), whereas in women, the correlation was moderate (r = -0.33; p < 0.001). Conversely, a strong positive correlation was observed between PhA and intracellular water (ICW) volume in women (r = 0.71; p < 0.001), while in men this association was weaker (r = 0.17; p < 0.05). The data indicate that PhA is significantly correlated with body fluid distribution and body composition. The key determinants differ by sex-fat mass, particularly visceral fat, plays a predominant role in men, while in women, muscle mass appears to be the dominant factor. PhA thus emerges as a valid, non-invasive marker of body composition, sensitive to changes in internal milieu, with potential clinical applications for assessing nutritional status and the patient's physiological condition. Keywords Bioelectrical impedance analysis " Phase angle " Body composition " Sex characteristics " Body water distribution.

这项观察性、描述性和横断面研究的目的是分析由生物电阻抗分析(BIA)确定的相位角(PhA)与健康成人身体成分参数之间的关系。该研究包括265名参与者(122名女性和143名男性),年龄在18-77岁之间,于2022年4月至2023年12月在布拉格的一家营养门诊进行了检查。使用Tanita MC-780 MA分析仪进行分段多频BIA,有8个电极,频率为5 kHz, 50 kHz和250 kHz。男性的平均PhA值显著高于女性(6.29°vs. 5.57°;p < 0.001)。在男性中观察到细胞外水与全身水比(ECW/TBW)与PhA之间存在很强的负相关(r = 0.78, p < 0.001),而在女性中,相关性为中度(r = -0.33, p < 0.001)。相反,在女性中,PhA与细胞内水(ICW)体积呈正相关(r = 0.71, p < 0.001),而在男性中,这种相关性较弱(r = 0.17, p < 0.05)。数据表明,PhA与体液分布和身体成分显著相关。关键的决定因素因性别而异——脂肪量,尤其是内脏脂肪,在男性中起主导作用,而在女性中,肌肉量似乎是主导因素。因此,PhA作为一种有效的、非侵入性的身体成分标记物,对体内环境的变化很敏感,在评估营养状况和患者生理状况方面具有潜在的临床应用价值。关键词:生物电阻抗分析;相角;人体组成;
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引用次数: 0
Nrf2 Overexpression in Spontaneously Hypertensive Rats Enhances Adipose Tissue Metabolism through Redox-Mediated Suppression of Mitochondrial Oxidative Phosphorylation. 自发性高血压大鼠Nrf2过表达通过氧化还原介导的线粒体氧化磷酸化抑制促进脂肪组织代谢
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
P Mlejnek, M Šimáková, J Šilhavý, T Mráček, J Houštěk, I Marková, M Hüttl, H Malínská, M Pravenec

The spontaneously hypertensive rat (SHR) is a widely used model of essential hypertension that also exhibits metabolic disturbances under specific conditions. Oxidative stress plays a central role in the pathogenesis of both hypertension and metabolic dysfunction, with the transcription factor Nrf2 regulating key antioxidant defenses. Here, we examined whether Nrf2 overexpression in the SHR improves adipose tissue metabolism. A mouse Nrf2 transgene under a universal promoter was markedly overexpressed in white adipose tissue, leading to increased insulin sensitivity, reduced saturated fatty acids, and higher n-3 polyunsaturated fatty acids in adipose membrane phospholipids. Transgenic rats also displayed reduced mitochondrial complex I levels, enhanced antioxidant enzyme activities, and decreased lipoperoxidation. Transcriptomic analysis revealed downregulation of oxidative phosphorylation genes. These findings suggest that Nrf2 overexpression confers antidiabetic and hypolipidemic effects in the SHR, potentially via redox-sensitive remodeling of adipose tissue metabolism. Key words: Nrf2 o Spontaneously hypertensive rat (SHR) o Oxidative stress o Adipose tissue o Metabolism o Mitochondrial function o Oxidative phosphorylation o Antioxidant defense o Insulin sensitivity o Fatty acids o transcriptomics o Transgenic rats o Gene expression.

自发性高血压大鼠(SHR)是一种广泛使用的原发性高血压模型,在特定条件下也表现出代谢紊乱。氧化应激在高血压和代谢功能障碍的发病机制中起着核心作用,转录因子Nrf2调节关键的抗氧化防御。在这里,我们研究了Nrf2在SHR中的过表达是否能改善脂肪组织代谢。在通用启动子下的Nrf2转基因小鼠在白色脂肪组织中显著过表达,导致胰岛素敏感性增加,饱和脂肪酸减少,脂肪膜磷脂中n-3多不饱和脂肪酸增加。转基因大鼠还表现出线粒体复合物I水平降低,抗氧化酶活性增强,脂质过氧化降低。转录组学分析显示氧化磷酸化基因下调。这些发现表明Nrf2过表达在SHR中具有降糖和降血脂的作用,可能是通过脂肪组织代谢的氧化还原敏感重构。关键词:Nrf2自发高血压大鼠(SHR)氧化应激脂肪组织代谢线粒体功能氧化磷酸化抗氧化防御胰岛素敏感性脂肪酸转录组学转基因大鼠基因表达
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引用次数: 0
Potential Effect of Trigonella Microgreens on Functional Parameters of HUVEC Cells in vitro. 微绿Trigonella对体外HUVEC细胞功能参数的潜在影响
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
T Jambor, Z Goc, K Tokarova, N Lukac

The growing popularity of microgreens is due to several health-promoting effects. Current evidence suggests a reduction in the risk of cardiovascular and neurodegenerative diseases, or anti-carcinogenic and anti-inflammatory effects. However, in vitro studies investigating cellular changes and molecular mechanisms are limited. Therefore, the use of various cell lines is required for a better understanding of microgreens' effects. In this study, the effect of Trigonella-foenum graecum L. microgreens (10 300 µg/mL) extract on morphological and functional changes in HUVEC cells were investigated. Basic cellular parameters such as mitochondrial activity (MTT assay), cell membrane integrity (CFDA-AM assay), and lysosomal activity (NR uptake) were evaluated after 24 h exposure to experimental ethanolic extract. In addition, the release of cytokine IL-6 was measured. Results revealed significant changes (p<0.05; p<0.01) in mitochondrial activity, followed by no defect in cell membrane integrity and non-significant changes in lysosomal activity of HUVEC cells. At the same time, some experimental doses of Trigonella slightly modulate IL-6 release, but showed no significant changes after 24 h exposure. Overall, our pilot study suggests the potential of Trigonella microgreens to modulate mitochondrial activity of HUVEC cells, without significant changes in cell membrane integrity, lysosomal activity, or IL-6 release. Key words Trigonella-foenum graecum L. " Microgreens " Cytokines " HUVEC cells.

微型蔬菜越来越受欢迎是由于几种促进健康的作用。目前的证据表明,它可以降低心血管和神经退行性疾病的风险,或具有抗癌和抗炎作用。然而,在体外研究细胞变化和分子机制是有限的。因此,为了更好地了解微绿菌的作用,需要使用不同的细胞系。本实验以10 300µg/mL三角铃草微绿提取物对HUVEC细胞形态和功能变化的影响为研究对象。在暴露于实验乙醇提取物24小时后,对线粒体活性(MTT法)、细胞膜完整性(CFDA-AM法)和溶酶体活性(NR摄取)等基本细胞参数进行评估。同时测定细胞因子IL-6的释放量。结果显示显著变化(p
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引用次数: 0
Effect of Muscle Contraction Under Caloric Restriction on Irisin and FGF21 Secretion in Mice. 热量限制下肌肉收缩对小鼠鸢尾素和FGF21分泌的影响。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-15
R Tanimura, H Watanabe, T Shirai, K Uemichi, T Iwata, T Takemasa

Combining diet and physical activity is known to be more effective for health than either intervention alone. Recent research has shown that skeletal muscle secretes myokines in response to exercise, which contribute to the adaptation of other organs to exercise. Therefore, we hypothesized that muscle adaptation by calorie restriction (CR) might enhance myokine responses to exercise. It is known that the myokine fibroblast growth factor-21 (FGF-21) secreted by skeletal muscle during exercise activates adipose tissue browning. We have already reported that irisin, a myokine that contributes to the metabolic activation of adipose tissue and weight loss, is secreted in response to muscle contraction by electrical stimulation (ES). Thus, we investigated the secretion of FGF21 and irisin upon the combination of ES with CR in this study. Mice were divided into four groups: control mice (Con), calorie restriction mice (CR), acute muscle contraction mice (ES), and acute muscle contraction after calorie restriction mice (CRES). After 1 week of acclimation, we subjected the mice to 60 % calorie restriction. After 2 weeks of CR, we performed ES. The results showed that the irisin expression level in serum was significantly increased by the combination of ES and CR, and an interaction between CR and ES was confirmed. FGF21 expression in serum was significantly decreased by CR. In conclusion, we confirm that irisin is a myokine whose secretion is increased synergistically by CR and muscle contraction. Keywords Muscle " Calorie restriction " Myokine " Irisin " FGF21.

众所周知,饮食和体育活动相结合比单独干预更有效。最近的研究表明,骨骼肌在运动时分泌肌因子,这有助于其他器官适应运动。因此,我们假设热量限制(CR)的肌肉适应可能会增强肌肉因子对运动的反应。众所周知,运动时骨骼肌分泌的肌因子成纤维细胞生长因子-21 (FGF-21)可激活脂肪组织褐变。我们已经报道了鸢尾素,一种有助于脂肪组织代谢激活和体重减轻的肌肉因子,是在电刺激(ES)肌肉收缩时分泌的。因此,我们在本研究中研究了ES与CR联合使用后FGF21和鸢尾素的分泌情况。小鼠分为4组:对照组(Con)、热量限制小鼠(CR)、急性肌肉收缩小鼠(ES)和热量限制后急性肌肉收缩小鼠(CRES)。经过1周的驯化后,我们对小鼠进行了60%的卡路里限制。CR 2周后,我们进行ES。结果表明,ES与CR联合使用可显著提高血清中鸢尾素的表达水平,证实了CR与ES之间的相互作用。综上所述,我们证实鸢尾素是一种肌因子,其分泌通过CR和肌肉收缩协同增加。肌肉;卡路里限制;肌因子;鸢尾素;
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引用次数: 0
Serum MicroRNA-196, -200 and -423 Improve Diagnostics and Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis. 血清MicroRNA-196、-200和-423提高胰腺导管腺癌与慢性胰腺炎的诊断和鉴别
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-02
P Škrha, A Hořínek, J Hajer, J Potočková, P Frič, J Bureš, M Anděl, J Škrha

Sustained poor survival rate in pancreatic ductal adenocarcinoma (PDAC) calls for an earlier diagnosis to assure curative treatment. New powerful biomarkers are necessary because the currently used CA19-9 is not sensitive enough to distinguish PDAC, especially from chronic pancreatitis (CP). Expressions of miRNA-21, -30 -192, -196, -200, and -423 were measured in 77 patients with PDAC, 26 patients with CP and 64 non-cancer/non-CP subjects (39 patients with type 2 diabetes mellitus and 25 control healthy persons). Eleven patients with PDAC had CP at the background. The expressions of all microRNAs were significantly 1.4-3.7 times higher in the PDAC group compared to non-cancer/non-CP subjects and 2.2-6.1 times higher compared to CP patients. No difference in miRNA expressions was found between diabetic and non-diabetic patients. CA19-9 did not distinguish CP from PDAC patients with the history of CP, whereas all six miRNAs were able to do it. Adding miR-196, -200 and -423 to current marker CA19-9 improved sensitivity by 7 % (to 93 %) and specificity by 8 % (to 89 %). MicroRNA-423 could significantly distinguish PDAC from CP with both sensitivity and specificity 96 %. Panel of six miRNAs could be used as reliable marker in differentiating PDAC from chronic pancreatitis with the most impressive difference in miR-196 and miR-423. Key words microRNA " Pancreatic ductal adenocarcinoma " Chronic pancreatitis " Biomarker " CA19-9.

胰腺导管腺癌(PDAC)的持续低生存率要求早期诊断以确保治愈治疗。由于目前使用的CA19-9不足以区分PDAC,特别是慢性胰腺炎(CP),因此需要新的强大的生物标志物。在77例PDAC患者、26例CP患者和64例非肿瘤/非CP患者(39例2型糖尿病患者和25例对照健康人)中检测miRNA-21、-30 -192、-196、-200和-423的表达。11例PDAC患者背景有CP。PDAC组所有microrna的表达量比非癌症/非CP组高1.4-3.7倍,比CP组高2.2-6.1倍。糖尿病患者与非糖尿病患者miRNA表达无差异。CA19-9不能区分CP和有CP病史的PDAC患者,而所有6种mirna都能做到这一点。将miR-196、-200和-423添加到当前的标记物CA19-9中,灵敏度提高7%(至93%),特异性提高8%(至89%)。MicroRNA-423能显著区分PDAC和CP,敏感性和特异性均为96%。6组mirna可作为区分PDAC与慢性胰腺炎的可靠标志物,其中miR-196和miR-423的差异最大。关键词:microRNA;胰腺导管腺癌;慢性胰腺炎;
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引用次数: 0
False-Positive Cardiac Troponin Elevations in Skeletal Muscle Disease: Clinical Relevance, Mechanisms, and Laboratory Approaches. 骨骼肌疾病中假阳性心肌肌钙蛋白升高:临床相关性、机制和实验室方法。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-02
D Rajdl, M Šolcová, J Racek, D Suchý, H Vimmerová, P Broz, P Prokop

Cardiac troponins are indispensable biomarkers for the diagnosis of acute myocardial infarction, but false-positive elevations that contradict the clinical picture remain a significant challenge in laboratory medicine. Analytical interferences may arise from macrotroponins, heterophile or anti-troponin antibodies, and the limited cardiac specificity of high-sensitivity troponin T (hs-cTnT) in skeletal muscle disease. Recent studies show that hs-cTnT is elevated in up to two-thirds of patients with myopathies, while high-sensitivity troponin I (hs-cTnI) is largely unaffected, underscoring the diagnostic advantage of hs-cTnI in this setting. A pragmatic diagnostic approach should combine clinical plausibility with stepwise laboratory testing. First, preanalytical factors such as sample mislabeling, fibrin clots, or hemolysis must be excluded and the measurement repeated. If the results remain incongruent, an alternative assay - ideally hs-cTnI - should be performed. Further evaluation may include heterophile-blocking reagents, polyethylene glycol precipitation to screen for macro-analytes, and, where available, confirmatory techniques such as gel filtration chromatography or immunoglobulin depletion (protein A/G). Although these strategies can help identify assay interference, there is no universally accepted gold standard. Awareness of false-positive elevations, careful interpretation of discordant troponin results, and effective collaboration between laboratories and clinicians are essential to prevent misdiagnosis and unnecessary interventions. Clear documentation of confirmed interferences further ensures safe patient management and provides guidance on which assays are reliable for future tests. Key words Cardiac troponin " Skeletal muscle disease " False-positive results " Analytical interference " Macrotroponin " Laboratory diagnostics.

心肌肌钙蛋白是诊断急性心肌梗死不可缺少的生物标志物,但与临床情况相矛盾的假阳性升高仍然是实验室医学的一个重大挑战。分析干扰可能来自大肌钙蛋白、嗜异性或抗肌钙蛋白抗体,以及骨骼肌疾病中高敏感性肌钙蛋白T (hs-cTnT)有限的心脏特异性。最近的研究表明,hs-cTnT在多达三分之二的肌病患者中升高,而高敏感性肌钙蛋白I (hs-cTnI)在很大程度上不受影响,强调了hs-cTnI在这种情况下的诊断优势。实用的诊断方法应结合临床合理性和逐步实验室检测。首先,必须排除分析前因素,如样品错误标记、纤维蛋白凝块或溶血,并重复测量。如果结果仍然不一致,则应进行另一种测定-理想的是hs-cTnI。进一步的评估可能包括异亲性阻断试剂,聚乙二醇沉淀法来筛选宏观分析物,以及在可用的情况下,验证技术,如凝胶过滤层析或免疫球蛋白消耗(蛋白A/G)。虽然这些策略可以帮助识别分析干扰,但没有普遍接受的金标准。意识到假阳性升高,仔细解释不一致的肌钙蛋白结果,以及实验室和临床医生之间的有效合作对于防止误诊和不必要的干预至关重要。明确记录确认的干扰进一步确保了患者管理的安全,并为未来检测的可靠分析提供了指导。【关键词】心肌肌钙蛋白;骨骼肌疾病;假阳性;
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引用次数: 0
Targeting of miR-93-5p/Mfn2 Axis Attenuates Lung Fibrosis in Rats With Acute Respiratory Distress Syndrome by Regulating Endoplasmic Reticulum Stress. 靶向miR-93-5p/Mfn2轴通过调节内质网应激减轻急性呼吸窘迫综合征大鼠肺纤维化
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-02
X Zhang, T Liu, Z Dai, Q Zhao, N An

High mortality rates among patients with acute respiratory distress syndrome (ARDS) have been linked to pulmonary fibrosis. MicroRNAs exhibit significant potential in modulating pulmonary fibrosis. However, the specific role and underlying mechanisms of miR-93-5p in the context of ARDS-associated pulmonary fibrosis remain largely unexplored. Mitofusin 2 (Mfn2) is a highly conserved transmembrane GTPase. Our previous study demonstrated that the upregulation of Mfn2 can inhibit pulmonary fibrosis in ARDS mice. In this investigation, we identified upstream miRNAs regulating Mfn2 using bioinformatics tools such as TargetScan, miRDB, and microT-CDS. Based on the expression levels of these miRNAs in lung tissue from rats with LPS-induced ARDS, miR-93-5p was selected as the focus of our research. We modulated miR-93-5p expression in ARDS rats via tail vein injection of a miR-93-5p antagomir. Thereafter, we conducted pathological staining and molecular assays to examine the impact of miR-93-5p on pulmonary fibrosis in ARDS rats and to elucidate its potential mechanisms. The results demonstrated that the expression of miR-93-5p was significantly upregulated in the lung tissue of ARDS rats. LPS-induced ARDS rats exhibited severe pulmonary fibrosis, inflammation, and strong endoplasmic reticulum (ER) stress. Furthermore, Mfn2 expression exhibited a negative correlation with miR-93-5p expression. Inhibition of miR-93-5p markedly upregulated Mfn2 expression, attenuated ER stress and lung inflammation, and decreased collagen deposition. In conclusion, the inhibition of miR-93-5p upregulated Mfn2 expression and attenuated ER stress, consequently ameliorating pulmonary fibrosis in ARDS rats. Key words Acute respiratory distress syndrome " miR-93-5p " Pulmonary fibrosis " Endoplasmic reticulum stress " Mitofusin 2.

急性呼吸窘迫综合征(ARDS)患者的高死亡率与肺纤维化有关。MicroRNAs在调节肺纤维化方面表现出显著的潜力。然而,miR-93-5p在ards相关肺纤维化中的具体作用和潜在机制在很大程度上仍未被探索。Mitofusin 2 (Mfn2)是一种高度保守的跨膜GTPase。我们前期研究表明上调Mfn2可抑制ARDS小鼠肺纤维化。在这项研究中,我们使用生物信息学工具,如TargetScan、miRDB和microT-CDS,确定了调控Mfn2的上游mirna。根据这些mirna在lps诱导的ARDS大鼠肺组织中的表达水平,我们选择miR-93-5p作为我们的研究重点。我们通过尾静脉注射miR-93-5p拮抗剂来调节ARDS大鼠的miR-93-5p表达。随后,我们通过病理染色和分子检测来检测miR-93-5p对ARDS大鼠肺纤维化的影响,并阐明其潜在机制。结果表明,miR-93-5p在ARDS大鼠肺组织中的表达明显上调。lps诱导的ARDS大鼠表现出严重的肺纤维化、炎症和强烈的内质网应激。此外,Mfn2表达与miR-93-5p表达呈负相关。抑制miR-93-5p可显著上调Mfn2表达,减轻内质网应激和肺部炎症,减少胶原沉积。综上所述,抑制miR-93-5p可上调Mfn2表达,减轻内质网应激,从而改善ARDS大鼠的肺纤维化。关键词:急性呼吸窘迫综合征;miR-93-5p;肺纤维化;内质网应激;
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引用次数: 0
Role of Esketamine in Attenuating Neuroinflammation and Improving Postoperative Cognitive Function via Autophagy Activation Through PARP1 Targeting. 艾氯胺酮通过PARP1靶向自噬激活减轻神经炎症和改善术后认知功能的作用。
IF 2 4区 医学 Q3 PHYSIOLOGY Pub Date : 2025-12-02
C Zhao, J Liu, S Zhao, P Liu, Z Li, Y Li, R Dong, X-L Wang

Postoperative cognitive dysfunction (POCD) substantially influences patient outcomes, with its pathophysiology potentially linked to neuroinflammation induced by surgical procedures and anesthesia. Previous research has indicated that esketamine may alleviate neuroinflammation. Therefore, elucidating the mechanisms through which esketamine modulates neuroinflammation to ameliorating POCD is crucial for advancing its clinical management. An in vivo model of POCD was established using C57BL/6J mice subjected to exploratory laparotomy. Cognitive performance was evaluated through the Morris water maze. Subsequently, hippocampal tissue samples were collected to measure changes in the levels of IL-1beta, IL-6, TNF-alpha, PARP1, SIRT1, LC3, and P62. In vitro experiments were performed using BV2 microglial cells treated with lipopolysaccharides (LPS) to induce inflammation and a PARP1 plasmid to create PARP1 overexpression (OvPARP1) models. These models were treated with esketamine, followed by assessment of changes in the previously mentioned indicators. Immunofluorescence microscopy was used to examine PARP1 expression, while transmission electron microscopy was used to analyze cellular autophagy. Exploratory laparotomy induced POCD and triggered neuroinflammation within the hippocampus of the mice. Treatment with esketamine alleviated POCD by inhibiting OvPARP1 expression and increasing SIRT1 levels, which promoted cellular autophagy and reduced neuroinflammation. Esketamine regulates the PARP1-SIRT1 pathway, thereby activating autophagy, reducing neuro-inflammation, and improving POCD. These findings provide novel insights into potential therapeutic strategies for the management of POCD. Key words Autophagy " Esketamine " Neuroinflammation " PARP1 " Postoperative cognitive dysfunction.

术后认知功能障碍(POCD)严重影响患者的预后,其病理生理学可能与外科手术和麻醉诱导的神经炎症有关。先前的研究表明,艾氯胺酮可以缓解神经炎症。因此,阐明艾氯胺酮通过调节神经炎症来改善POCD的机制对于推进其临床管理至关重要。采用开腹探查小鼠C57BL/6J建立POCD体内模型。通过Morris水迷宫评估认知能力。随后,收集海马组织样本,测量il -1 β、IL-6、tnf - α、PARP1、SIRT1、LC3和P62水平的变化。体外实验采用脂多糖(LPS)处理BV2小胶质细胞诱导炎症,用PARP1质粒构建PARP1过表达(OvPARP1)模型。这些模型用艾氯胺酮处理,然后评估上述指标的变化。免疫荧光显微镜检测PARP1表达,透射电镜检测细胞自噬情况。剖腹探查诱发POCD并引发小鼠海马神经炎症。艾氯胺酮治疗通过抑制OvPARP1表达和增加SIRT1水平,促进细胞自噬和减少神经炎症来缓解POCD。艾氯胺酮调节PARP1-SIRT1通路,从而激活自噬,减少神经炎症,改善POCD。这些发现为POCD的潜在治疗策略提供了新的见解。关键词自噬埃氯胺酮神经炎症PARP1术后认知功能障碍
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引用次数: 0
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