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Development and temporal-validation of prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture among adults with cerebral palsy 针对脑瘫成人肺炎、呼吸衰竭/塌陷和骨折 5 年风险的预后模型的开发和时间验证。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 Epub Date: 2025-01-22 DOI: 10.1016/j.advms.2025.01.007
Daniel G. Whitney

Purpose

Pneumonia, respiratory failure, and fracture are common and highly burdensome for adults with cerebral palsy (CP). To date, there are no clinically friendly tools to assess individualized risk of these outcomes for adults with CP. The objective was to develop and validate prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture for adults with CP.

Patients and methods

This single medical center retrospective cohort study used medical records from January 1, 2012 till June 1, 2024 from adults ≥18 years old with CP. The development cohort (n ​= ​1520) included those with a start date of follow-up from January 1, 2015 till December 31, 2015 and evidence of being treated at the medical center for ≥3 years prior to day 0. The 5-year risk of outcomes was modelled using logistic regression and variations of the following predictors that were collected during the 3-year baseline: age, sex, Whitney Comorbidity Index, pneumonia, respiratory failure/collapse, fracture, and asthma/COPD. Discrimination (c-statistic) and calibration statistics assessed the model's performance. Decision curve analysis assessed the model's clinical utility. The models were validated in a temporal validation cohort, whose start date of follow-up was January 1, 2016 to May 31, 2019 (n ​= ​529).

Results

The prognostic models had good discrimination (c-statistic ​= ​0.76–0.78), good-to-excellent calibration, and demonstrated superior clinical utility in identifying true positives and true negatives. All models demonstrated temporal validation.

Conclusions

Prognostic models for 5-year risk of outcomes were developed and temporally validated for adults with CP using measures that can be easily collected from medical records.
目的:肺炎、呼吸衰竭和骨折是脑瘫(CP)患者常见且负担沉重的疾病。到目前为止,还没有临床友好的工具来评估成人CP患者这些结果的个体化风险。目的是开发和验证成人CP患者5年肺炎、呼吸衰竭/衰竭和骨折风险的预后模型。这项单医疗中心回顾性队列研究使用了2012年1月1日至2024年6月1日的医疗记录,这些记录来自年龄≥18岁的CP患者。发展队列(n= 1520)包括从2015年1月1日至2015年12月31日开始随访的患者,以及在第0天之前在医疗中心接受治疗≥3年的证据。使用逻辑回归和3年基线期间收集的以下预测因子的变化对5年结局风险进行建模:年龄、性别、惠特尼合并症指数、肺炎、呼吸衰竭/衰竭、骨折和哮喘/COPD。判别(c-statistic)和校正统计量评估模型的性能。决策曲线分析评估模型的临床效用。这些模型在一个时间验证队列中进行验证,该队列的随访开始日期为2016年1月1日至2019年5月31日(n=529)。结果:预后模型具有良好的鉴别性(c-statistic=0.76-0.78),良好至优异的校准,在鉴别真阳性和真阴性方面具有卓越的临床实用性。所有模型均证明了时间有效性。结论:利用从医疗记录中容易收集到的措施,开发了成人CP 5年预后风险模型,并对其进行了暂时验证。
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引用次数: 0
Metabolic dysfunction-associated steatotic liver disease - A new indication for sodium-glucose Co-transporter-2 inhibitors 代谢功能障碍相关性脂肪肝--钠-葡萄糖共转运体-2 抑制剂的新适应症。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-09-10 DOI: 10.1016/j.advms.2024.09.001
Grzegorz Procyk , Jakub Jaworski , Aleksandra Gąsecka , Krzysztof J. Filipiak , Josip A. Borovac

Metabolic dysfunction–associated steatotic liver disease (MASLD) has been proposed as a new name for the previous non-alcoholic fatty liver disease (NAFLD). There are some differences between MASLD and NAFLD, e.g., diagnostic criteria. MASLD is a hepatic steatosis without harmful alcohol consumption and is caused by metabolic factors. The prevalence of MASLD varies amongst different populations. The change in lifestyle plays a fundamental role in MASLD management, while there is no registered pharmacotherapy in this indication. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to have a beneficial effect on hepatic steatosis, hence, they have been widely investigated as potential therapeutics in MASLD. In this review, we aimed to thoroughly summarize current evidence from original research about the effects of SGLT2i use on MASLD. Almost all discussed studies advocate using SGLT2i in MASLD because of their beneficial effects. It includes the loss of body weight, which is beneficial per se, and the improvement in hepatic parameters. Most importantly, steatosis reduction has been observed in patients using SGLT2i. We highly recommend further research in this field, which we believe will eventually lead to a new indication for SGLT2i, i.e., MASLD.

代谢功能障碍相关性脂肪性肝病(MASLD)已被提出作为之前的非酒精性脂肪肝(NAFLD)的新名称。MASLD 与 NAFLD 在诊断标准等方面存在一些差异。非酒精性脂肪肝是一种肝脏脂肪变性,没有饮酒的危害,是由代谢因素引起的。MASLD在不同人群中的发病率各不相同。改变生活方式在 MASLD 的治疗中起着根本性的作用,但目前还没有针对这一适应症的注册药物疗法。钠-葡萄糖共转运体 2 抑制剂(SGLT2i)被认为对肝脏脂肪变性有好处,因此作为 MASLD 的潜在治疗药物被广泛研究。在这篇综述中,我们旨在全面总结目前有关使用 SGLT2i 对 MASLD 的影响的原创性研究证据。几乎所有讨论过的研究都主张在 MASLD 中使用 SGLT2i,因为它们具有有益的作用。其中包括减轻体重(这本身就是有益的)和改善肝脏参数。最重要的是,在使用 SGLT2i 的患者中观察到脂肪变性减轻。我们强烈建议在这一领域开展进一步研究,相信最终会为 SGLT2i 带来新的适应症,即 MASLD。
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引用次数: 0
Single-cell sequencing analysis confirms the association of ANRIL with the increased smooth muscle cell proliferation and migration gene signatures in pulmonary artery hypertension in silico 单细胞测序分析证实 ANRIL 与肺动脉高压中平滑肌细胞增殖和迁移基因特征的相关性
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-04-16 DOI: 10.1016/j.advms.2024.04.002
Yan Li, Yan-Tong Zhang, Bing Han, Lan Xue, Yan Wei, Ge Li

Purpose

Smooth muscle cell (SMC) dysregulation is part of the pathological basis of pulmonary artery hypertension (PAH). We aimed to explore the heterogeneity of SMCs in PAH.

Methods

The profile GSE210248 was obtained from NCBI Gene Expression Omnibus, containing the scRNA-seq data of pulmonary arteries (PA) from three patients with PAH and three healthy donors. After quality control, normalization, and dimension reduction, cell clustering analysis was performed. Differential expression analysis and functional enrichment analysis were carried out successively in smooth muscle cells (SMCs). The enrichment scores of cell cycle and cell migration gene sets in SMCs were calculated. Then, the Spearman correlation coefficients between antisense non-coding RNA in the INK4 locus (ANRIL) expression and two gene sets were computed.

Results

Eight cell clusters were identified in PA from samples. The proportion of SMCs was increased in PAH samples. SMCs were divided into five subclusters with diverse biological functions. Muscle contraction-related SMC1 was decreased, while extracellular matrix organization-related SMC2, immune and inflammatory response-related SMC4 and SMC5 were increased in PAH samples compared with healthy donors. The enrichment scores of cell cycle and cell migration gene sets in SMCs were higher in PAH samples than in donors. ANRIL was down-regulated significantly in PAH samples and was negatively related to the scores of two gene sets.

Conclusion

SMCs exhibited significant heterogeneity in PAH. The altered abilities of SMC proliferation and migration in PAH were associated with ANRIL expression.

目的平滑肌细胞(SMC)失调是肺动脉高压(PAH)病理基础的一部分。我们的目的是探索 PAH 中平滑肌细胞的异质性。方法从 NCBI 基因表达总库中获得了 GSE210248 资料,其中包含 3 名 PAH 患者和 3 名健康供体的肺动脉(PA)scRNA-seq 数据。经过质量控制、归一化和降维处理后,进行了细胞聚类分析。先后对平滑肌细胞(SMC)进行了差异表达分析和功能富集分析。计算了平滑肌细胞中细胞周期和细胞迁移基因组的富集得分。然后计算了 INK4 位点反义非编码 RNA(ANRIL)表达与两个基因组之间的 Spearman 相关系数。PAH 样本中 SMC 的比例有所增加。SMC 被分为五个亚群,具有不同的生物学功能。与健康供体相比,PAH样本中与肌肉收缩相关的SMC1减少,而与细胞外基质组织相关的SMC2、与免疫和炎症反应相关的SMC4和SMC5增加。PAH 样本中 SMCs 细胞周期和细胞迁移基因集的富集得分高于供体。ANRIL 在 PAH 样本中明显下调,并与两个基因组的得分呈负相关。PAH中SMC增殖和迁移能力的改变与ANRIL的表达有关。
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引用次数: 0
An evaluation of the effect of the use of platelet-rich fibrin on tonsillectomy results 评估使用富血小板纤维蛋白对扁桃体切除术效果的影响。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-09-18 DOI: 10.1016/j.advms.2024.09.004
Aslıhan Oflaz Çapar, Emre Solguntekin, Kerem Kökoğlu, Mehmet Ilhan Şahin

Purpose

The aim of this study was to investigate the effect of liquid platelet-rich fibrin (PRF) during tonsillectomy on postoperative results.

Patients and methods

This study included 41 patients who underwent tonsillectomy between April 2022 and January 2023. Liquid-PRF at a dose of 1 ​cc was injected to three different points of one of the tonsil fossae, selected at random intraoperatively. The same amount of physiological saline was injected to the symmetrical points on the opposite tonsil fossa using the same size injector. Pain, wound healing, and bleeding were evaluated on postoperative days 1, 7, and 14. The data of both sides were compared statistically as the study and control sides.

Results

The pain scores were the highest for both sides on postoperative day 1, and gradually decreased in the following days, with no significant difference determined between the sides (p ​> ​0.05). Wound healing rates in the 1st week and 2 ​nd ​week were similar for both sides. Although there were more patients who have 100 ​% epithelization in the PRF group on the postoperative day 14, the difference between the groups was not statistically significant (p ​> ​0.05).

Conclusions

The injection of PRF following tonsillectomy had no significant effect on postoperative pain, wound healing, or bleeding.
目的:本研究旨在探讨扁桃体切除术中液态富血小板纤维蛋白(PRF)对术后效果的影响:本研究纳入了在 2022 年 4 月至 2023 年 1 月期间接受扁桃体切除术的 41 名患者。在术中随机选择扁桃体窝的三个不同点注射 1cc 剂量的液体-PRF。使用相同大小的注射器,在对侧扁桃体窝的对称点注射相同剂量的生理盐水。术后第 1、7 和 14 天对疼痛、伤口愈合和出血情况进行评估。将两侧的数据作为研究侧和对照侧进行统计比较:结果:术后第 1 天两侧疼痛评分最高,随后几天逐渐降低,两侧疼痛评分无明显差异(P>0.05)。第 1 周和第 2 周的伤口愈合率两侧相似。虽然术后第 14 天 PRF 组上皮化生率达 100% 的患者较多,但组间差异无统计学意义(P>0.05):扁桃体切除术后注射 PRF 对术后疼痛、伤口愈合和出血无明显影响。
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引用次数: 0
Effect of nonsurgical periodontal therapy with additional photodynamic therapy on the level of MMP-9 and TIMP-1 in GCF in chronic periodontitis patients-a preliminary pilot study 非手术牙周治疗附加光动力疗法对慢性牙周炎患者 GCF 中 MMP-9 和 TIMP-1 水平的影响--一项初步试点研究。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-07-24 DOI: 10.1016/j.advms.2024.07.009
Ewa Dolińska , Anna Skurska , Małgorzata Pietruska , Violetta Dymicka-Piekarska , Robert Milewski , Anton Sculean

Purpose

Matrix metalloproteinases (MMPs) catalyze degradation of extracellular matrix proteins. The activity of MMPs is controlled by tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the MMP-9/TIMP-1 ratio has been linked with chronic periodontitis (CP). Photodynamic therapy (PDT) uses visible light, photosensitizer and oxygen to eradicate pathogens. The aim of the study was to evaluate the presence of MMP-9 and TIMP-1 in gingival crevicular fluid (GCF) in chronic periodontitis patients before and after nonsurgical periodontal therapy with additional PDT.

Methods

Nineteen patients, each with CP, were included in the study. After periodontal examination one site with a probing depth (PD) ​≥ ​4 ​mm was selected. The patients received scaling and root planing (SRP) with additional PDT by means of HELBO® diode minilaser. Prior to treatment, and after 3 and 6 months, the following parameters were estimated from the same site: PD, gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP) and sulcus fluid flow rate (SFFR). The levels of MMP-9 and TIMP-1 in GCF were determined.

Results

Compared to baseline, the levels of MMP-9 and TIMP-1 did not show statistically significant differences after 3 and 6 months. According to Spearman's rank correlations, MMP-9 was positively correlated with SFFR at all time points. PD, CAL and PI showed a statistically significant decrease compared to baseline (p ​< ​0.001). SFFR decreased but not significantly.

Conclusion

Nonsurgical periodontal therapy in conjunction with PDT was clinically effective but it had no effect on the levels of MMP-9 and TIMP-1 in GCF.

目的:基质金属蛋白酶(MMPs)可催化细胞外基质蛋白的降解。金属蛋白酶的活性受金属蛋白酶组织抑制剂(TIMPs)的控制。MMP-9/TIMP-1比例失调与慢性牙周炎(CP)有关。光动力疗法(PDT)使用可见光、光敏剂和氧气来消灭病原体。本研究的目的是评估慢性牙周炎患者在接受非手术牙周治疗和附加光动力疗法前后牙龈缝隙液(GCF)中 MMP-9 和 TIMP-1 的含量:本研究共纳入 19 名慢性牙周炎患者。牙周检查后,选择一个探诊深度(PD)≥ 4 毫米的部位。患者在接受洗牙和根面平整(SRP)治疗的同时,还使用 HELBO® 二极管微型激光器进行局部光疗。在治疗前以及治疗 3 个月和 6 个月后,对同一部位的下列参数进行了估算:PD、牙龈退缩(GR)、临床附着水平(CAL)、牙菌斑指数(PI)、探诊出血量(BOP)和龈沟液流率(SFFR)。结果发现,与基线相比,MMP-9和TIMP-1在牙龈龈沟液中的水平有所下降:结果:与基线相比,MMP-9 和 TIMP-1 的水平在 3 个月和 6 个月后的差异无统计学意义。根据斯皮尔曼等级相关性,MMP-9 在所有时间点均与 SFFR 呈正相关。与基线相比,PD、CAL 和 PI 均出现了统计学意义上的显著下降(p 结论:非手术牙周治疗与 PDT 联合使用临床效果显著,但对 GCF 中的 MMP-9 和 TIMP-1 水平没有影响。
{"title":"Effect of nonsurgical periodontal therapy with additional photodynamic therapy on the level of MMP-9 and TIMP-1 in GCF in chronic periodontitis patients-a preliminary pilot study","authors":"Ewa Dolińska ,&nbsp;Anna Skurska ,&nbsp;Małgorzata Pietruska ,&nbsp;Violetta Dymicka-Piekarska ,&nbsp;Robert Milewski ,&nbsp;Anton Sculean","doi":"10.1016/j.advms.2024.07.009","DOIUrl":"10.1016/j.advms.2024.07.009","url":null,"abstract":"<div><h3>Purpose</h3><p>Matrix metalloproteinases (MMPs) catalyze degradation of extracellular matrix proteins. The activity of MMPs is controlled by tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the MMP-9/TIMP-1 ratio has been linked with chronic periodontitis (CP). Photodynamic therapy (PDT) uses visible light, photosensitizer and oxygen to eradicate pathogens. The aim of the study was to evaluate the presence of MMP-9 and TIMP-1 in gingival crevicular fluid (GCF) in chronic periodontitis patients before and after nonsurgical periodontal therapy with additional PDT.</p></div><div><h3>Methods</h3><p>Nineteen patients, each with CP, were included in the study. After periodontal examination one site with a probing depth (PD) ​≥ ​4 ​mm was selected. The patients received scaling and root planing (SRP) with additional PDT by means of HELBO® diode minilaser. Prior to treatment, and after 3 and 6 months, the following parameters were estimated from the same site: PD, gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP) and sulcus fluid flow rate (SFFR). The levels of MMP-9 and TIMP-1 in GCF were determined.</p></div><div><h3>Results</h3><p>Compared to baseline, the levels of MMP-9 and TIMP-1 did not show statistically significant differences after 3 and 6 months. According to Spearman's rank correlations, MMP-9 was positively correlated with SFFR at all time points. PD, CAL and PI showed a statistically significant decrease compared to baseline (p ​&lt; ​0.001). SFFR decreased but not significantly.</p></div><div><h3>Conclusion</h3><p>Nonsurgical periodontal therapy in conjunction with PDT was clinically effective but it had no effect on the levels of MMP-9 and TIMP-1 in GCF.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 362-367"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1896112624000439/pdfft?md5=90f50aed205014667e68e158055748e7&pid=1-s2.0-S1896112624000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipidomic approach to identify Escherichia coli and Shigella spp. by matrix-assisted laser desorption/ionization mass spectrometry 利用基质辅助激光解吸电离质谱法鉴定大肠杆菌和志贺氏杆菌的脂质组学方法
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-04-24 DOI: 10.1016/j.advms.2024.04.005
Adrian Arendowski

Purpose

Escherichia coli (E. coli) and Shigella species, being highly similar, present a challenge for differentiation using classical methods such as phenotyping, 16S rRNA sequencing, or protein profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The paper proposes a method for identifying E. coli, S. flexneri, S. sonnei, and S. boydii by augmenting the Bruker Biotyper database with reference spectra of lipid profiles obtained using MALDI MS in the positive mode.

Materials/methods

Lipid extracts were made from cultured E. coli, S. flexneri, S. sonnei and S. boydii using the Bligh & Dyer protocol. MALDI MS spectra in positive ion mode were performed for the extracts. Reference spectra were created from 30 spectra for each bacterium and added to the Bruker Biotyper database.

Results

Identification of bacteria based on lipid profiles in the Biotyper database gave correct results with scores above 2.49. Statistical analysis of the results by Partial Least Squares-Discriminant Analysis (PLS-DA) showed that it is possible to correctly differentiate the microorganisms studied using the lipidomic approach. A panel of six m/z values was proposed for which the value of the area under the ROC curve is 1, thus enabling the identification of E. coli and S. flexneri with 100 ​% accuracy.

Conclusions

Identification of bacteria from lipid fingerprints obtained by the MALDI MS technique is possible and may become a useful tool in the future, especially for microorganisms that are difficult to distinguish by other methods.

目的 大肠埃希氏菌(E. coli)和志贺氏菌(Shigella)物种高度相似,使用传统方法(如表型分析、16S rRNA 测序或使用基质辅助激光解吸电离质谱(MALDI MS)进行蛋白质分析)进行鉴别是一项挑战。本文提出了一种鉴别大肠杆菌、柔性链球菌、宋内氏菌和波氏杆菌的方法,即利用 MALDI MS 在正向模式下获得的脂质图谱的参考光谱来增强布鲁克 Biotyper 数据库。在正离子模式下对提取物进行 MALDI MS 图谱分析。结果根据 Biotyper 数据库中的脂质图谱对细菌进行鉴定,结果正确率在 2.49 以上。通过偏最小二乘判别分析(PLS-DA)对结果进行的统计分析表明,使用脂质体方法可以正确区分所研究的微生物。结论通过 MALDI MS 技术获得的脂质指纹鉴定细菌是可能的,而且将来可能成为一种有用的工具,特别是对于用其他方法难以区分的微生物。
{"title":"Lipidomic approach to identify Escherichia coli and Shigella spp. by matrix-assisted laser desorption/ionization mass spectrometry","authors":"Adrian Arendowski","doi":"10.1016/j.advms.2024.04.005","DOIUrl":"10.1016/j.advms.2024.04.005","url":null,"abstract":"<div><h3>Purpose</h3><p><em>Escherichia coli</em> (<em>E. coli</em>) and <em>Shigella</em> species, being highly similar, present a challenge for differentiation using classical methods such as phenotyping, 16S rRNA sequencing, or protein profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The paper proposes a method for identifying <em>E. coli</em>, <em>S. flexneri</em>, <em>S. sonnei</em>, and <em>S. boydii</em> by augmenting the Bruker Biotyper database with reference spectra of lipid profiles obtained using MALDI MS in the positive mode.</p></div><div><h3>Materials/methods</h3><p>Lipid extracts were made from cultured <em>E. coli, S. flexneri, S. sonnei</em> and <em>S. boydii</em> using the Bligh &amp; Dyer protocol. MALDI MS spectra in positive ion mode were performed for the extracts. Reference spectra were created from 30 spectra for each bacterium and added to the Bruker Biotyper database.</p></div><div><h3>Results</h3><p>Identification of bacteria based on lipid profiles in the Biotyper database gave correct results with scores above 2.49. Statistical analysis of the results by Partial Least Squares-Discriminant Analysis (PLS-DA) showed that it is possible to correctly differentiate the microorganisms studied using the lipidomic approach. A panel of six <em>m/z</em> values was proposed for which the value of the area under the ROC curve is 1, thus enabling the identification of <em>E. coli</em> and <em>S. flexneri</em> with 100 ​% accuracy.</p></div><div><h3>Conclusions</h3><p>Identification of bacteria from lipid fingerprints obtained by the MALDI MS technique is possible and may become a useful tool in the future, especially for microorganisms that are difficult to distinguish by other methods.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 238-247"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Angiopoietin-like 4 facilitates human aortic smooth muscle cell phenotype switch and dysfunctions through the PI3K/Akt signaling in aortic dissection 血管生成素样 4 在主动脉夹层中通过 PI3K/Akt 信号转导促进人类主动脉平滑肌细胞表型转换和功能障碍。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-09-24 DOI: 10.1016/j.advms.2024.09.006
Wei He , Quan Zheng , Tingfang Zou , Wei Yan , Xue Gao , Chunle Wang , Yaoyao Xiong

Purpose

Vascular smooth muscle cell (VSMC) phenotype switch and dysfunctions have been reported to participate in aortic dissection (AD) progression. This study was aimed to investigate the role of angiopoietin-like 4 (ANGPTL4) in regulating VSMCs phenotype switch.

Materials and methods

Key genes were analyzed in AD using public datasets, and it was found that the central differential gene ANGPTL4 was up-regulated in AD. The KEGG signaling pathway annotation was performed to validate the associated pathways, and the expression of ANGPTL4 was verified using multiple datasets and clinical samples. Furthermore, the specific functions of ANGPTL4 on platelet-derived growth factor-BB (PDGF-BB)-treated human aortic smooth muscle cell (HASMC) phenotypes were investigated. The dynamic effects of ANGPTL4 and core signaling antagonists on HASMC phenotypes were examined.

Results

Hub gene ANGPTL4 was significantly up-regulated in AD. ANGPTL4 was linked to the PI3K/Akt signaling, angiogenesis, and neovascularization and remodeling. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotypes, including promoted cell viability and migration, decreased contractile VSMC markers α-SMA and SM22α, elevated ECM degradation markers MMP-2 and MMP-9, and promoted phosphorylation of PI3K and Akt. ANGPTL4 knockdown partially abolished PDGF-BB-induced contractile/synthetic VSMCs imbalance and HASMC dysfunctions. Furthermore, in ANGPTL4-overexpressing HASMCs pre-treated with PDGF-BB, the PI3K/Akt signaling inhibitor LY294002 also partially eliminated the effects caused by the PDGF-BB treatment and ANGPTL4 overexpression.

Conclusions

ANGPTL4 is significantly up-regulated in AD. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotype switch and dysfunctions, which might be involved in the PI3K/Akt signaling.
目的:据报道,血管平滑肌细胞(VSMC)表型转换和功能障碍参与了主动脉夹层(AD)的进展。本研究旨在探讨血管生成素样4(ANGPTL4)在调控血管平滑肌细胞表型转换中的作用:利用公开数据集分析了AD中的关键基因,发现中心差异基因ANGPTL4在AD中上调。通过KEGG信号通路注释验证了相关通路,并利用多个数据集和临床样本验证了ANGPTL4的表达。此外,还研究了ANGPTL4对血小板衍生生长因子-BB(PDGF-BB)处理的人主动脉平滑肌细胞(HASMC)表型的特定功能。研究了 ANGPTL4 和核心信号拮抗剂对 HASMC 表型的动态影响:结果:AD的枢纽基因ANGPTL4明显上调。ANGPTL4与PI3K/Akt信号传导、血管生成、新生血管形成和重塑有关。ANGPTL4 的过表达进一步增强了 PDGF-BB 对 HASMC 表型的影响,包括促进细胞活力和迁移、降低收缩性 VSMC 标志物 α-SMA 和 SM22α、提高 ECM 降解标志物 MMP-2 和 MMP-9,以及促进 PI3K 和 Akt 的磷酸化。敲除 ANGPTL4 可部分消除 PDGF-BB 诱导的收缩/合成 VSMC 失衡和 HASMC 功能障碍。此外,在用PDGF-BB预处理的ANGPTL4过表达的HASMC中,PI3K/Akt信号抑制剂LY294002也部分消除了PDGF-BB处理和ANGPTL4过表达造成的影响:结论:ANGPTL4在AD中明显上调。结论:ANGPTL4在AD中明显上调,ANGPTL4过表达进一步增强了PDGF-BB对HASMC表型转换和功能障碍的影响,这可能与PI3K/Akt信号转导有关。
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引用次数: 0
Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU 利用 miR-193a-5p 和 5-FU 靶向 MMP16 降低胃癌细胞株的转移能力
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-09-26 DOI: 10.1016/j.advms.2024.09.008
Tahani Ahmad Almatrafi , Natrayan Lakshmaiya , Hailah M. Almohaimeed , Srikumar Chakravarthi , Ali H. Amin , Ayman Jafer , Amany I. Almars , Ammar A. Basabrain , Youssef S. Alghamdi , Mohamed J. Saadh , Reza Akhavan-Sigari

Purpose

Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC).

Materials/methods

Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients.

Results

The current study found that while MMP16 expression increased in GC patients (P ​< ​0.0001), miR-193a-5p expression significantly decreased (P ​< ​0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P ​< ​0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p.

Conclusions

These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.
目的:microRNAs与化疗药物联合应用可有效治疗多种癌症。本研究试图探讨基质金属蛋白酶16(MMP16)和miR-193a-5p在胃癌(GC)发病机制中的功能:65例手术患者(其中15例接受了5-氟尿嘧啶(5-FU)治疗)提供了GC和邻近的非癌组织。然后,使用 qPCR 评估 GC 细胞中 MMP16 和 miR-193a-5p 的表达水平。使用 qRT-PCR 和 Western 印迹法评估了 miR-193a-5p 和 5-FU 给药对 MMP16 mRNA 表达的影响。还进行了 MTT 和划痕试验,以评估它们对细胞活力和迁移的影响。此外,还利用 MTT 试验进行了挽救实验。使用流式细胞术计算了细胞凋亡率。最后,还评估了 MMP16 和 miR-193a-5p 与患者临床病理特征的关系:结果:目前的研究发现,虽然 MMP16 在 GC 患者(PConclusions.)中的表达增加,但 miR-193a-5p 在 GC 患者中的表达却没有增加:这些研究结果表明,miR-193a-5p 与 5-FU 联用可下调 MMP16 在 GC 中的表达,从而抑制肿瘤生长。
{"title":"Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU","authors":"Tahani Ahmad Almatrafi ,&nbsp;Natrayan Lakshmaiya ,&nbsp;Hailah M. Almohaimeed ,&nbsp;Srikumar Chakravarthi ,&nbsp;Ali H. Amin ,&nbsp;Ayman Jafer ,&nbsp;Amany I. Almars ,&nbsp;Ammar A. Basabrain ,&nbsp;Youssef S. Alghamdi ,&nbsp;Mohamed J. Saadh ,&nbsp;Reza Akhavan-Sigari","doi":"10.1016/j.advms.2024.09.008","DOIUrl":"10.1016/j.advms.2024.09.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC).</div></div><div><h3>Materials/methods</h3><div>Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients.</div></div><div><h3>Results</h3><div>The current study found that while MMP16 expression increased in GC patients (P ​&lt; ​0.0001), miR-193a-5p expression significantly decreased (P ​&lt; ​0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P ​&lt; ​0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p.</div></div><div><h3>Conclusions</h3><div>These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 463-473"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evolution of splenomegaly in liver cirrhosis: Simulation using an electronic circuit 肝硬化脾肿大的演变:利用电子电路进行模拟。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI: 10.1016/j.advms.2024.08.001
Jae Cheol Jung, Shin-Young Park, Kyeong Deok Kim, Woo Young Shin, Keon-Young Lee

Purpose

The evolution of splenomegaly in patients with liver cirrhosis remains largely unknown. In this study, we followed the changes in splenic volume and established the natural course of splenomegaly. We developed an electronic circuit that simulated splenoportal circulation and identified the underlying hemodynamic mechanisms.

Materials and methods

This retrospective observational study included 93 patients with cirrhosis. Splenic volumes were measured in imaging studies at 6-month intervals and normalized by the ratio of each patient's maximum volume during follow-up (%Vmax). An electronic simulation model was constructed using software and realized on a breadboard.

Results

Overall, the %Vmax increased from 0.77 ​± ​0.21 to a maximum of 1.00 ​± ​0.00 (p ​< ​0.001) during a median follow-up of 23 (3–162) months and then decreased to 0.84 ​± ​0.18 (p ​< ​0.001) during the next 9 (3–132) months. No interventional radiology procedure was performed to improve hepatic fibrosis and portal hypertension. The evolution of %Vmax showed single-peaked symmetry. An electronic simulation model showed that the upslope of the evolution curve was dependent on the increased intrahepatic vascular resistance and portal hypertension, whereas the downslope was dependent on the decreased portosystemic shunt (PSS) resistance.

Conclusions

Splenomegaly in cirrhotic patients aggravated over a period of 23 months and then regressed spontaneously to its initial volume. Electronic simulation of splenoportal circulation showed that splenic enlargement was due to the advancement of liver cirrhosis and portal hypertension, whereas its regression was due to the development of a PSS.

目的:肝硬化患者脾脏肿大的演变过程在很大程度上仍不为人所知。在这项研究中,我们跟踪了脾脏体积的变化,并确定了脾脏肿大的自然病程。我们开发了模拟脾门循环的电子电路,并确定了潜在的血液动力学机制:这项回顾性观察研究包括 93 名肝硬化患者。每隔 6 个月通过影像学检查测量脾脏体积,并以随访期间每位患者最大体积的比率(%Vmax)进行归一化。使用软件构建了一个电子模拟模型,并在面包板上实现了该模型:总体而言,在 23(3 - 162)个月的中位随访期间,最大容积百分比从 0.77 ± 0.21 增加到最大值 1.00 ± 0.00(p < 0.001),然后在接下来的 9(3 - 132)个月期间降至 0.84 ± 0.18(p < 0.001)。没有进行介入放射学手术来改善肝纤维化和门静脉高压。Vmax%的变化呈现单峰对称性。电子模拟模型显示,演变曲线的上坡取决于肝内血管阻力和门静脉高压的增加,而下坡则取决于门静脉分流(PSS)阻力的降低:结论:肝硬化患者的脾肿大在 23 个月内不断加重,然后自然消退至初始体积。对脾门静脉循环的电子模拟显示,脾脏肿大是由于肝硬化和门静脉高压的发展所致,而脾脏肿大的消退则是由于 PSS 的发展所致。
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引用次数: 0
Periodontal disease in patients with thyroid diseases: A systematic review with meta-analysis 甲状腺疾病患者的牙周病:系统回顾与荟萃分析。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1016/j.advms.2024.06.003
Martyna Ortarzewska , Kacper Nijakowski , Jakub Jankowski , Nadia Sawicka-Gutaj , Marek Ruchała , Anna Surdacka

Purpose

The imbalance of thyroid hormones affects the metabolic activity of various tissues, including periodontium. Also, autoimmune diseases present an increased tendency to suffer from periodontal disease. Therefore, our systematic review was designed to answer the question "Is there a relationship between thyroid diseases and periodontal disease?".

Materials and methods

Following the inclusion and exclusion criteria, 10 studies were included in this systematic review using the databases PubMed, Scopus and Web of Science (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines).

Results

Based on the meta-analysis, patients with thyroid diseases (especially with hypothyroidism) demonstrated significantly worse periodontal status than systemically healthy controls. Moreover, according to the cross-sectional studies, 5.74 ​% of periodontitis patients reported the concomitance of thyroid diseases.

Conclusions

In summary, the included studies suggest a potential relationship between thyroid diseases and periodontal disease. However, further research is necessary to reliably assess the oral health in patients with hypothyroidism and hyperthyroidism.

目的:甲状腺激素失衡会影响包括牙周在内的各种组织的新陈代谢活动。此外,自身免疫性疾病也会增加患牙周病的几率。因此,我们的系统综述旨在回答 "甲状腺疾病与牙周病之间是否存在关系?按照纳入和排除标准,使用 PubMed、Scopus 和 Web of Science 数据库(根据系统综述和荟萃分析首选报告项目声明指南)将 10 项研究纳入本系统综述:根据荟萃分析,甲状腺疾病(尤其是甲状腺功能减退症)患者的牙周状况明显差于全身健康的对照组。此外,根据横断面研究,5.74%的牙周炎患者报告患有甲状腺疾病:总之,纳入的研究表明甲状腺疾病与牙周病之间存在潜在的关系。然而,要可靠地评估甲状腺功能减退症和甲状腺功能亢进症患者的口腔健康状况,还需要进一步的研究。
{"title":"Periodontal disease in patients with thyroid diseases: A systematic review with meta-analysis","authors":"Martyna Ortarzewska ,&nbsp;Kacper Nijakowski ,&nbsp;Jakub Jankowski ,&nbsp;Nadia Sawicka-Gutaj ,&nbsp;Marek Ruchała ,&nbsp;Anna Surdacka","doi":"10.1016/j.advms.2024.06.003","DOIUrl":"10.1016/j.advms.2024.06.003","url":null,"abstract":"<div><h3>Purpose</h3><p>The imbalance of thyroid hormones affects the metabolic activity of various tissues, including periodontium. Also, autoimmune diseases present an increased tendency to suffer from periodontal disease. Therefore, our systematic review was designed to answer the question \"Is there a relationship between thyroid diseases and periodontal disease?\".</p></div><div><h3>Materials and methods</h3><p>Following the inclusion and exclusion criteria, 10 studies were included in this systematic review using the databases PubMed, Scopus and Web of Science (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines).</p></div><div><h3>Results</h3><p>Based on the meta-analysis, patients with thyroid diseases (especially with hypothyroidism) demonstrated significantly worse periodontal status than systemically healthy controls. Moreover, according to the cross-sectional studies, 5.74 ​% of periodontitis patients reported the concomitance of thyroid diseases.</p></div><div><h3>Conclusions</h3><p>In summary, the included studies suggest a potential relationship between thyroid diseases and periodontal disease. However, further research is necessary to reliably assess the oral health in patients with hypothyroidism and hyperthyroidism.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 289-295"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1896112624000348/pdfft?md5=8e181ec9883ed138b637abc40202c530&pid=1-s2.0-S1896112624000348-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Advances in medical sciences
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