Advances in medical sciences最新文献_第5页

Optimizing in vitro lung cancer therapy with folate-conjugated polydopamine-coated liposomes loaded with gemcitabine 叶酸偶联多多巴胺包被脂质体负载吉西他滨优化肺癌体外治疗。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.advms.2025.02.001

Chandramohan Govindasamy , Muhammad Ibrar Khan , Chitrakani Bose , Muruganantham Bharathi , Shamini Senthilkumar , Parthasarathy Surya

Purpose

Surface-altered, targeted nanocarriers play crucial roles in chemotherapy. Incorporating ligands into polymers may alter their chemical composition, potentially compromising their drug storage and encapsulation capacity. Polydopamine (PDA) is a novel, biocompatible, and versatile agent for producing targeted nanoparticles that serve as a base for conjugating specific ligands to non-reactive polymeric nanocarriers. This investigation aimed to evaluate whether gemcitabine (GEM)-loaded liposomes conjugated with PDA could enhance cancer treatment.

Materials and methods

A series of liposomes, named plain GEM, GEM@FA, and GEM@FA/PDA, was designed. Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS) were used to confirm the presence of PDA coating and folic acid (FA) and PDA conjugations. Cellular uptake, cytotoxicity, and cell death were evaluated using biochemical and flow cytometric assays.

Results

Compared to typical liposomes, GEM@FA/PDA liposomes were smaller, more stable, and exhibited a spherical shape with excellent cellular uptake. GEM@FA and GEM@FA/PDA liposomes showed significantly higher cytotoxicity against lung cancer (H1299) cells compared to GEM liposomes and pure GEM solution at all concentrations, while causing much less cytotoxicity to normal cells (NIH3T3).

Conclusions

GEM@FA/PDA liposomes demonstrated enhanced cancer-fighting effectiveness while minimizing harm to healthy tissues, making them a promising approach for chemotherapy.

目的：表面修饰的靶向纳米载体在化疗中发挥着重要作用。将配体掺入聚合物可能会改变其化学组成，从而潜在地影响其药物储存和封装能力。聚多巴胺（PDA）是一种新型的、生物相容性的、多功能的药物，用于生产靶向纳米颗粒，作为将特定配体偶联到非反应性聚合物纳米载体的基础。本研究旨在评估负载吉西他滨（GEM）的脂质体与PDA结合是否可以增强癌症治疗。材料与方法：设计了一系列脂质体，分别命名为plain GEM、GEM@FA和GEM@FA/PDA。透射电镜（TEM）、傅里叶红外光谱（FTIR）和x射线光电子能谱（XPS）证实了PDA涂层以及叶酸（FA）和PDA偶联物的存在。使用生化和流式细胞术测定细胞摄取、细胞毒性和细胞死亡。结果：与典型脂质体相比，GEM@FA/PDA脂质体更小，更稳定，呈球形，具有良好的细胞摄取性。与GEM脂质体和纯GEM溶液相比，GEM@FA和GEM@FA/PDA脂质体在所有浓度下对肺癌（H1299）细胞的细胞毒性显著提高，而对正常细胞的细胞毒性要小得多（NIH3T3）。结论：GEM@FA/PDA脂质体显示出增强的抗癌效果，同时最大限度地减少对健康组织的伤害，使其成为一种有希望的化疗方法。

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引用次数: 0

The association between circulating irisin, osteocalcin and FGF21 levels with anthropometric characteristics and blood lipid profile in young obese male subjects 年轻肥胖男性受试者中循环鸢尾素、骨钙素和FGF21水平与人体测量特征和血脂之间的关系

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-31 DOI: 10.1016/j.advms.2025.01.010

Sema Sayharman, Muaz Belviranlı, Nilsel Okudan

Purpose

Myokines secreted from skeletal muscle such as irisin, osteokines secreted from bone such as osteocalcin, and hepatokines secreted from the liver such as fibroblast growth factor 21 (FGF21) play a role in the regulation of metabolic homeostasis. However, the changes that occur in obesity and the interaction between them have not been fully explained. Therefore, this study aimed to compare irisin, osteocalcin and FGF21 levels in young obese males against individuals with normal body weight and to reveal the possible relationship between them and with anthropometric measurements and blood lipid profile.

Materials and methods

This single-center study included 28 Turkish young males aged 20–29 years: 14 obese participants with a body mass index (BMI) between 30.0 and 34.9 and 14 healthy controls with a BMI between 18.5 and 24.9. Anthropometric, and body composition parameters, blood lipid profile, and irisin, osteocalcin and FGF21 levels of groups were measured. Correlation analyses were performed between irisin, osteocalcin, and FGF21 and other measured parameters.

Results

Circulating irisin, osteocalcin and FGF21 levels were significantly higher in the obese group than in the control group (p < 0.05). Correlation analysis showed that irisin was positively correlated with total cholesterol, triglycerides and low density lipoprotein-cholesterol (LDL-C) and FGF21 was positively correlated with total cholesterol and LDL-C (p < 0.05). Positive correlation between irisin and osteocalcin, FGF21 and osteocalcin and FGF21 and irisin was observed (p < 0.05).

Conclusions

Irisin, osteocalcin, and FGF21 have a potential role in the pathophysiology of obesity and related metabolic diseases due to their interactions.

目的：骨骼肌分泌的肌因子如鸢尾素，骨骼分泌的骨因子如骨钙素，肝脏分泌的肝因子如成纤维细胞生长因子21 （FGF21）在代谢稳态调节中发挥作用。然而，肥胖中发生的变化以及它们之间的相互作用尚未得到充分解释。因此，本研究旨在比较年轻肥胖男性与正常体重个体的鸢尾素、骨钙素和FGF21水平，并揭示它们与人体测量和血脂之间的可能关系。材料和方法：本单中心研究纳入28名年龄在20-29岁的土耳其年轻男性：14名体重指数（BMI）在30.0-34.9之间的肥胖参与者和14名体重指数在18.5-24.9之间的健康对照组。测量各组的人体测量、体成分参数、血脂、鸢尾素、骨钙素和FGF21水平。鸢尾素、骨钙素与FGF21等测量参数进行相关性分析。结果：肥胖组循环鸢尾素、骨钙素、FGF21水平明显高于对照组（p < 0.05）。相关分析显示，鸢尾素与总胆固醇、甘油三酯、低密度脂蛋白胆固醇（LDL-C）呈正相关，FGF21与总胆固醇、LDL-C呈正相关（p < 0.05）。鸢尾素与骨钙素、FGF21与骨钙素、FGF21与鸢尾素呈正相关（p < 0.05）。结论：鸢尾素、骨钙素和FGF21通过相互作用在肥胖和相关代谢疾病的病理生理中具有潜在的作用。

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引用次数: 0

Inhibition of TRPM7 by glutathione decreases oxidant and apoptotic action of cisplatin through the downregulation of Ca2+ and Zn2+ in glioblastoma cells 谷胱甘肽抑制TRPM7可通过下调胶质母细胞瘤细胞中Ca2+和Zn2+来降低顺铂的氧化和凋亡作用。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-30 DOI: 10.1016/j.advms.2025.01.008

Kemal Ertilav , Mustafa Nazıroğlu

Purpose

Cisplatin (CiSP)-mediated stimulation of TRPM7 may induce oxidant and apoptotic activities through the upregulation of Ca²⁺, apoptosis, and reactive oxygen species (ROS) in glioblastoma (DBTRG-05MG) cells, whereas inhibition of TRPM7 by the antioxidant glutathione (GSH) may reduce the observed increases in DBTRG-05MG. The aim of the study was to examine how TRPM7 activation stimulates DBTRG-05MG cell death but also how it inhibits the effects of TRPM7 antagonists (GSH and carvacrol, CRV) via altering ROS toxicity and apoptosis.

Method

In the DBTRG-05MG, 5 groups were established: control, GSH (10 mM for 2 h), CiSP (25 μM for 24 h), CiSP + GSH, and CiSP + CRV (200 μM for 24 h).

Results

The amounts of cytosolic free Ca²⁺ were further increased in the CiSP group by the stimulation of TRPM7 (naltriben), even though the GSH and CRV treatments caused them to decrease in the cells. The amounts of mitochondrial membrane dysfunction, ROS, death cell, apoptosis, free zinc ion, and caspase-3, -8, and -9 in the cells were higher in the CiSP than in the control and GSH, although their amounts were lower in the CiSP + GSH and CiSP + CRV than in the CiSP only. The CiSP-induced decreases in cell viability and GSH concentrations were increased by GSH incubation.

Conclusions

The stimulation of TRPM7 increased the anticancer action of CiSP, although its inhibition decreased the amount of CiSP-induced oxidative stress and DBTRG-05MG deaths through the treatment of GSH and CRV. TRPM7 stimulation could be considered a potential tumor killer channel through oxidative glioblastoma damage caused by CiSP.

目的：顺铂（CiSP）介导的TRPM7刺激可能通过上调胶质母细胞瘤（DBTRG-05MG）细胞中的Ca2+、凋亡和活性氧（ROS）来诱导氧化和凋亡活性，而抗氧化剂谷胱甘肽（GSH）抑制TRPM7可能会减少DBTRG-05MG的增加。该研究的目的是研究TRPM7激活如何刺激DBTRG-05MG细胞死亡，以及它如何通过改变ROS毒性和细胞凋亡来抑制TRPM7拮抗剂（GSH和carvacrol， CRV）的作用。方法：在DBTRG-05MG中建立5组：对照组、GSH （10 mM, 2h）、CiSP （25 μM, 24h）、CiSP+GSH、CiSP+CRV （200 mM, 24h）。结果：CiSP组胞质游离Ca2+的数量在TRPM7（钠triben）的刺激下进一步增加，尽管GSH和CRV处理导致它们在细胞中减少。细胞中线粒体膜超极化、ROS、死亡细胞、凋亡、游离锌离子和caspase-3、-8、-9的数量在CiSP中高于对照和GSH，但CiSP+GSH和CiSP+CRV的数量低于CiSP。GSH孵育后，cisp诱导的细胞活力和GSH浓度下降。结论：刺激TRPM7可增强CiSP的抗癌作用，但其抑制作用通过GSH和CRV的治疗降低了CiSP诱导的氧化应激和DBTRG-05MG死亡的数量。通过CiSP引起的氧化性胶质母细胞瘤损伤，TRPM7刺激可被认为是一个潜在的肿瘤杀伤通道。

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引用次数: 0

Novel factors of cisplatin resistance in epithelial ovarian tumours 卵巢上皮性肿瘤顺铂耐药的新因素。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-27 DOI: 10.1016/j.advms.2025.01.005

Pavol Harvanik , Martina Šemeláková , Zuzana Solárová , Peter Solár

Ovarian tumours are these days one of the biggest oncogynecological problems. In addition to surgery, the treatment of ovarian cancer includes also chemotherapy in which platinum preparations are one of the most used chemotherapeutic drugs. The principle of antineoplastic effects of cisplatin (cis-diamminedichloroplatinum(II), CDDP) is its binding to the DNA and the formation of adducts. While DNA adducts induce the process of apoptosis, or inhibit the process of DNA replication, which prevents further division of tumour cells, various molecular mechanisms can reverse this process. On the other hand, with increasing scientific knowledge, it is becoming clearer that chemotherapy resistance is a very complex process. In this regard, factors and the amount of their expression may regulate the effect of resistance to chemotherapy. This review focuses on new molecular mechanisms and factors such as mitochondrial dynamics, epithelial-mesenchymal transition (EMT), cluster of differentiation, exosomes and others, that could be involved in the emergence of CDDP resistance.

卵巢肿瘤是当今最大的妇科肿瘤问题之一。除手术外，卵巢癌的治疗还包括化疗，其中铂制剂是最常用的化疗药物之一。顺铂（顺-二胺二氯铂，CDDP）抗肿瘤作用的原理是其与DNA结合并形成加合物。DNA加合物可以诱导细胞凋亡过程，或抑制DNA复制过程，从而阻止肿瘤细胞进一步分裂，但多种分子机制可以逆转这一过程。另一方面，随着科学知识的增加，化疗耐药是一个非常复杂的过程，这一点越来越清楚。在这方面，因子及其表达量可能调节化疗耐药的效果。本文综述了可能参与CDDP耐药产生的线粒体动力学、上皮-间质转化（EMT）、分化簇、外泌体等新的分子机制和因素。

引用次数: 0

Circadian and autophagy markers correlate with poor prognosis in meningioma patients 昼夜节律和自噬标记与脑膜瘤患者预后不良有关

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-23 DOI: 10.1016/j.advms.2025.01.006

Keng-Liang Kuo , Shu-Jyuan Chang , Cheng Yu Tsai , Yen-Shuo Huang , Aij-Lie Kwan , Chee-Yin Chai

Purpose

Patients with meningiomas mostly present good outcomes and optimal prognosis, but different grades of tumors have very different symptoms and recurrence rates. Therefore, effective diagnosis is crucial for early intervention and controlling tumor development. Circadian cycle and autophagy have both been proven to be related to neoplasm formation and pathogenesis; however, there is limited exploration and discussion on the relationships between the circadian cycle and autophagy in patients with meningiomas. This study was undertaken to elucidate the relationship between two autophagy markers (Beclin1, LC3B) and one circadian marker (NR1D1) with clinicopathological parameters in patients with meningiomas.

Materials and methods

Clinicopathological data of 124 enrolled patients were collected. Tissue-sectioned slides were analyzed via immunohistochemical stains and the relationship between the markers was evaluated.

Results

Individually low expression of NR1D1 and Beclin 1 was associated with better prognosis, lower pathological grade, and longer survival. Although correlation analysis showed that NR1D1, Beclin 1 and LC3B were related to each other. However, the dual marker NR1D1-/Beclin 1- was effective in predicting good prognosis in meningiomas, whereas NR1D1-/LC3B- was not.

Conclusion

NR1D1 and Beclin 1 could be adopted as a single marker or coupled as a combined marker to predict meningioma prognoses, pathological grades, and survival. This study provides insights into the association between autophagy and circadian cycles and may benefit future elucidation of molecular mechanisms.

目的：脑膜瘤患者大多预后良好，但不同级别肿瘤的症状和复发率差异很大。因此，有效的诊断对早期干预和控制肿瘤发展至关重要。生物周期和自噬都被证明与肿瘤的形成和发病有关；然而，关于脑膜瘤患者的昼夜周期与自噬之间的关系，目前的探索和讨论有限。本研究旨在阐明脑膜瘤患者两种自噬标志物（Beclin1、LC3B）和一种昼夜节律标志物（NR1D1）与临床病理参数的关系。材料与方法：收集124例入组患者的临床病理资料。通过免疫组织化学染色分析组织切片，并评估标记物之间的关系。结果：NR1D1和Beclin 1单独低表达与预后较好、病理分级较低、生存期较长相关。尽管相关分析显示NR1D1、Beclin 1和LC3B三者之间存在相关性。然而，双标记NR1D1-/Beclin 1-能有效预测脑膜瘤的良好预后，而NR1D1-/LC3B-则不能。结论：NR1D1和Beclin 1可单独或联合作为预测脑膜瘤预后、病理分级及生存的指标。这项研究为自噬和昼夜周期之间的关系提供了见解，并可能有助于未来阐明分子机制。

{"title":"Circadian and autophagy markers correlate with poor prognosis in meningioma patients","authors":"Keng-Liang Kuo , Shu-Jyuan Chang , Cheng Yu Tsai , Yen-Shuo Huang , Aij-Lie Kwan , Chee-Yin Chai","doi":"10.1016/j.advms.2025.01.006","DOIUrl":"10.1016/j.advms.2025.01.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Patients with meningiomas mostly present good outcomes and optimal prognosis, but different grades of tumors have very different symptoms and recurrence rates. Therefore, effective diagnosis is crucial for early intervention and controlling tumor development. Circadian cycle and autophagy have both been proven to be related to neoplasm formation and pathogenesis; however, there is limited exploration and discussion on the relationships between the circadian cycle and autophagy in patients with meningiomas. This study was undertaken to elucidate the relationship between two autophagy markers (Beclin1, LC3B) and one circadian marker (NR1D1) with clinicopathological parameters in patients with meningiomas.</div></div><div><h3>Materials and methods</h3><div>Clinicopathological data of 124 enrolled patients were collected. Tissue-sectioned slides were analyzed via immunohistochemical stains and the relationship between the markers was evaluated.</div></div><div><h3>Results</h3><div>Individually low expression of NR1D1 and Beclin 1 was associated with better prognosis, lower pathological grade, and longer survival. Although correlation analysis showed that NR1D1, Beclin 1 and LC3B were related to each other. However, the dual marker NR1D1-/Beclin 1- was effective in predicting good prognosis in meningiomas, whereas NR1D1-/LC3B- was not.</div></div><div><h3>Conclusion</h3><div>NR1D1 and Beclin 1 could be adopted as a single marker or coupled as a combined marker to predict meningioma prognoses, pathological grades, and survival. This study provides insights into the association between autophagy and circadian cycles and may benefit future elucidation of molecular mechanisms.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 103-108"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035836","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

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

Advances in medical sciences

Pub 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

Safety and efficacy of therapeutic plasma exchange in pediatric neuro-immunological diseases 血浆置换治疗小儿神经免疫疾病的安全性和有效性。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-15 DOI: 10.1016/j.advms.2025.01.003

Magdalena Błasiak , Przemysław Korohoda , Katarzyna Zachwieja , Dorota Drożdż , Aleksandra Gergont , Karina Madej-Świątkowska , Monika Miklaszewska

Purpose

Therapeutic plasma exchange (TPE) is the treatment of choice in various neuro-immunological disorders in pediatric populations. This study assesses the safety and efficacy of TPE in this demographic.

Materials and methods

A single-center, retrospective cohort study involving pediatric patients who experienced neuro-immunological events and underwent TPE procedures at a tertiary referral center was conducted.

Results

The study included 81 patients (Guillain-Barre: 65, polyneuropathies: 5, myasthenia gravis: 8, multiple sclerosis: 3), undergoing collectively 360 TPE procedures. Fresh frozen plasma (FFP) was used in 76.1 % of the TPE procedures. Adverse events (AEs) occurred in 50 % of TPEs using FFP compared to 39.5 % without. For procedures with at least two AEs, the rates were 24.5 % with FFP vs 8.1 % without. Incidence of allergic AEs was significantly higher in the FFP group (94.2 % of TPE with at least one AE) compared to those without FFP (47.2 %). Serious AE accounted for 1.2 % of TPE procedures and 2.5 % of patients. Effectiveness evaluations using a scale developed for this study and the Hughes Functional Grading Scale showed no significant clinical pre-treatment differences. After completing the treatment, children in the polyneuropathies group had the most severe clinical condition, and the largest relative improvement in clinical status was in the myasthenia gravis group.

Conclusions

TPE conducted by filtration is an effective and safe therapy for pediatric neuro-immunological diseases, with benefits outweighing the risks of complications. The use of FFP in therapy increases the probability of AE by 27 %, and significantly raises the risk of allergic and multiple AEs.

目的：治疗性血浆置换（TPE）是儿科人群中各种神经免疫疾病的治疗选择。本研究评估了TPE在这一人群中的安全性和有效性。材料和方法：一项单中心、回顾性队列研究，涉及在三级转诊中心经历神经免疫事件并接受TPE手术的儿科患者。结果：81例患者（吉兰-巴雷综合征65例，多发性神经病变5例，重症肌无力8例，多发性硬化症3例）共接受了360例TPE手术。76.1%的TPE手术采用新鲜冷冻血浆（FFP）。与未使用FFP的39.5%相比，使用FFP的tpe中有50%发生不良事件（ae）。对于至少有两次ae的手术，有FFP的发生率为24.5%，而没有FFP的发生率为8.1%。FFP组过敏性不良事件的发生率（94.2%）明显高于无FFP组（47.2%）。严重AE占TPE手术的1.2%，占患者的2.5%。使用为本研究开发的量表和Hughes功能分级量表进行的有效性评估显示，临床治疗前无显著差异。治疗结束后，多神经病变组患儿临床状况最严重，重症肌无力组患儿临床状况相对改善最大。结论：滤过式TPE治疗小儿神经免疫疾病是一种安全有效的治疗方法，其益处大于并发症的风险。使用FFP治疗可使AE的发生概率增加27%，并显著增加过敏和多发AE的发生风险。

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引用次数: 0

Investigation of circulating natural autoantibodies against ANXA1 and MYC as potential biomarkers in hepatocellular carcinoma 抗ANXA1和MYC的循环天然自身抗体作为肝细胞癌潜在生物标志物的研究。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-15 DOI: 10.1016/j.advms.2025.01.004

Jiaxin Wang , Siqi Liu , Xuan Zhang

Purpose

In this study, we examined novel autoantibodies targeting tumor-associated antigens (TAAs) as biomarkers for clinical assessment of hepatocellular carcinoma (HCC) in a Chinese population.

Methods and methods

A total of 119 patients with HCC and 130 healthy control (HC) volunteers who were age and gender matched were enrolled. The levels of circulating IgG antibodies were detected using an enzyme-linked immunosorbent test (ELISA) developed in-house with linear peptide antigens derived from Annexin A1(ANXA1) and proto-oncogene protein (MYC). The significant level was set at P < 0.025 as two tests were performed.

Results

In comparison to the HC group, plasma level of ANXA1 autoantibodies was significantly elevated in HCC patients (t = −3.174, P = 0.002) but the change of plasma MYC autoantibody levels failed to reach the significance level (P > 0.025). There was a significant increase in these two plasma IgG autoantibodies in male HCC patients (ANXA1: t = −3.590, P < 0.001; MYC: t = −2.706, P = 0.007). Pearson correlation analysis demonstrated that both anti-ANXA1 and anti-MYC IgG levels had a positive correlation with BCLC staging (both P < 0.025) but a negative correlation with plasma albumin (Alb) (both P < 0.025). The area under the ROC curve (AUC) values were 0.613 for anti-ANXA1 IgG assay and 0.567 for anti-MYC IgG assay. The anti-ANAXA1 IgG assay showed a high sensitivity of 31.4 % against the specificity of 90.0 % for detection of BCLC stages C + D.

Conclusions

Plasma anti-ANXA1 and anti-MYC autoantibodies are likely to serve as a potential biomarker for clinical assessment of HCC prognosis, particularly in male patients.

目的：在这项研究中，我们检测了靶向肿瘤相关抗原（TAAs）的新型自身抗体作为中国人群肝细胞癌（HCC）临床评估的生物标志物。方法和方法：共纳入119例HCC患者和130例年龄和性别匹配的健康对照（HC）志愿者。采用酶联免疫吸附试验（ELISA）检测循环IgG抗体水平，该试验采用源自膜联蛋白A1（ANXA1）和原癌基因蛋白（MYC）的线性肽抗原。结果：HCC患者血浆中ANXA1自身抗体水平较HC组显著升高（t=-3.174, P = 0.002），而MYC自身抗体水平变化未达到显著水平（P = 0.025）。在男性HCC患者中，这两种血浆IgG自身抗体显著升高（ANXA1: t=-3.590, p）。结论：血浆抗ANXA1和抗myc自身抗体可能作为HCC临床预后评估的潜在生物标志物，尤其是在男性患者中。

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引用次数: 0

Downregulation and inhibition of TRPM2 calcium channel prevent oxidative stress-induced endothelial dysfunction in the EA.hy926 endothelial cells model - Preliminary studies 下调和抑制TRPM2钙通道可预防EA.hy926内皮细胞模型中氧化应激诱导的内皮功能障碍——初步研究

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-06 DOI: 10.1016/j.advms.2025.01.002

Wioletta Arendt , Klaudia Piekarska , Marta Hałas-Wiśniewska , Magdalena Izdebska , Alina Grzanka , Maciej Gagat

Purpose

Proper functioning of the endothelial barrier is crucial for cardiovascular system homeostasis. Oxidative stress can lead to endothelial dysfunction (ED), damaging lipids, proteins, and DNA. Reactive oxygen species also increase cytoplasmic Ca²⁺ levels, activating transient receptor potential melastatin 2 (TRPM2), a membrane non-selective calcium channel. The study aimed to assess TRPM2's significance in vascular endothelial cells' response to oxidative stress and the potential use of TRPM2 direct and indirect inhibitors in the prevention of oxidative stress-induced ED.

Materials and methods

EA.hy926 endothelial cells were exposed to hydrogen peroxide for 24 h to mimic oxidative stress conditions. To assess the significance of TRPM2 in the response of EA.hy926 cells to hydrogen peroxide TRPM2 siRNA as well as direct (N-(p-Amylcinnamoyl)anthranilic acid, flufenamic acid) and indirect (3-aminobenzamide, 3,4-dihydro-5[4-(1-piperidinyl)butyl]-1(2H)-isoquinolinone) TRPM2 inhibitors were tested.

Results

Results showed that hydrogen peroxide-induced ED is alleviated by TRPM2 downregulation. Moreover, preincubation of cells with both direct and indirect TRPM2 inhibitors for 30 min before hydrogen peroxide treatment reduces its negative effects on cell viability, cell migration, and junctional proteins.

Conclusions

The obtained results suggest that TRPM2 channel may be a potential target in therapy and prevention of cardiovascular diseases connected with oxidative stress-induced ED. However, further research is needed for clinical applications of direct and indirect TRPM2 inhibitors.

目的：内皮屏障的正常功能对心血管系统的稳态至关重要。氧化应激可导致内皮功能障碍（ED），损害脂质、蛋白质和DNA。活性氧也增加细胞质Ca2+水平，激活瞬时受体电位美拉抑素2 (TRPM2)，这是一种膜非选择性钙通道。本研究旨在评估TRPM2在血管内皮细胞对氧化应激反应中的意义，以及TRPM2直接和间接抑制剂在预防氧化应激诱导ed中的潜在应用。材料和方法：将EA.hy926内皮细胞暴露在过氧化氢环境中24小时，模拟氧化应激条件。为了评估TRPM2在EA.hy926细胞对过氧化氢TRPM2 siRNA以及直接（N-（对氨基肉桂基）苯甲酸、氟芬那酸）和间接（3-氨基苯甲酰胺、3,4-二氢-5[4-（1-哌替啶基）丁基]-1(2H)-异喹啉酮）TRPM2抑制剂反应中的意义。结果：过氧化氢诱导的ED可通过下调TRPM2得到缓解。此外，在过氧化氢处理前，将细胞与直接和间接TRPM2抑制剂一起预孵养30分钟，可以减少其对细胞活力、细胞迁移和连接蛋白的负面影响。结论：上述结果提示TRPM2通道可能是治疗和预防氧化应激性ED相关心血管疾病的潜在靶点，但TRPM2直接和间接抑制剂的临床应用还需进一步研究。

{"title":"Downregulation and inhibition of TRPM2 calcium channel prevent oxidative stress-induced endothelial dysfunction in the EA.hy926 endothelial cells model - Preliminary studies","authors":"Wioletta Arendt , Klaudia Piekarska , Marta Hałas-Wiśniewska , Magdalena Izdebska , Alina Grzanka , Maciej Gagat","doi":"10.1016/j.advms.2025.01.002","DOIUrl":"10.1016/j.advms.2025.01.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Proper functioning of the endothelial barrier is crucial for cardiovascular system homeostasis. Oxidative stress can lead to endothelial dysfunction (ED), damaging lipids, proteins, and DNA. Reactive oxygen species also increase cytoplasmic Ca<sup>2+</sup> levels, activating transient receptor potential melastatin 2 (TRPM2), a membrane non-selective calcium channel. The study aimed to assess TRPM2's significance in vascular endothelial cells' response to oxidative stress and the potential use of TRPM2 direct and indirect inhibitors in the prevention of oxidative stress-induced ED.</div></div><div><h3>Materials and methods</h3><div>EA.hy926 endothelial cells were exposed to hydrogen peroxide for 24 h to mimic oxidative stress conditions. To assess the significance of TRPM2 in the response of EA.hy926 cells to hydrogen peroxide TRPM2 siRNA as well as direct (N-(p-Amylcinnamoyl)anthranilic acid, flufenamic acid) and indirect (3-aminobenzamide, 3,4-dihydro-5[4-(1-piperidinyl)butyl]-1(2H)-isoquinolinone) TRPM2 inhibitors were tested.</div></div><div><h3>Results</h3><div>Results showed that hydrogen peroxide-induced ED is alleviated by TRPM2 downregulation. Moreover, preincubation of cells with both direct and indirect TRPM2 inhibitors for 30 min before hydrogen peroxide treatment reduces its negative effects on cell viability, cell migration, and junctional proteins.</div></div><div><h3>Conclusions</h3><div>The obtained results suggest that TRPM2 channel may be a potential target in therapy and prevention of cardiovascular diseases connected with oxidative stress-induced ED. However, further research is needed for clinical applications of direct and indirect TRPM2 inhibitors.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 62-78"},"PeriodicalIF":2.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942466","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

Clinical value of CEUS with tumour marker monitoring in evaluating the prognosis of HCC after MWA 超声造影联合肿瘤标志物监测对肝癌MWA术后预后评价的临床价值。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-02 DOI: 10.1016/j.advms.2025.01.001

Qiang Guo , Yang Yu , Ruyun Ye , Zhiliang Huang , Tingting Shi

Purpose

This study aims to evaluate the prognostic value of contrast-enhanced ultrasound (CEUS) combined with tumour markers in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA).

Methods

MWA patients with HCC were divided into good prognosis (n = 75) and poor prognosis (n = 69) groups. The levels of alpha-fetoprotein (AFP), carbohydrate antigen (CA19-9), and carcinoembryonic antigen (CEA) before and after MWA were analysed using an independent sample t-test. The correlation between prognosis, ablation lesion area, and tumour marker levels were analysed by Pearson's correlation. The diagnostic power of the ablation lesion area combined with tumour marker levels for the prognosis of patients with MWA was analysed using receiver operating characteristic (ROC) curves.

Results

The levels of AFP, CA19-9, and CEA in the good prognosis group were significantly lower than those in the poor prognosis group (all P < 0.001). The levels of all tumour markers were significantly negatively correlated with the prognosis of patients who underwent MWA (all r < 0, P < 0.001) and positively correlated with the area of tumour-ablated lesions (r > 0, P < 0.001). Moreover, the diagnostic efficacy of CEUS combined with tumour markers for the prognosis of patients who underwent MWA was significantly higher than that of either single diagnostic modality.

Conclusions

CEUS combined with tumour marker monitoring can effectively improve the accuracy of prognostic diagnosis in patients with MWA and provide a reference for timely and reasonable treatment and therapeutic evaluation.

目的：本研究旨在评价超声造影（CEUS）联合肿瘤标志物在肝细胞癌（HCC）微波消融（MWA）患者中的预后价值。方法：将MWA合并HCC患者分为预后良好组（n = 75）和预后不良组（n = 69）。采用独立样本t检验分析MWA前后甲胎蛋白（AFP）、碳水化合物抗原（CA19-9）、癌胚抗原（CEA）水平。采用Pearson相关分析预后、消融病灶面积与肿瘤标志物水平的相关性。采用受试者工作特征（ROC）曲线分析消融病灶面积结合肿瘤标志物水平对MWA患者预后的诊断能力。结果：预后良好组患者AFP、CA19-9、CEA水平显著低于预后不良组（P均< 0.001）。所有肿瘤标志物水平与MWA患者预后呈显著负相关（均r < 0, P < 0.001），与肿瘤消融灶面积呈正相关（均r < 0, P < 0.001）。此外，超声造影联合肿瘤标志物对MWA患者预后的诊断效果显著高于任何一种单一诊断方式。结论：超声造影联合肿瘤标志物监测可有效提高MWA患者预后诊断的准确性，为及时合理的治疗和疗效评价提供参考。

{"title":"Clinical value of CEUS with tumour marker monitoring in evaluating the prognosis of HCC after MWA","authors":"Qiang Guo , Yang Yu , Ruyun Ye , Zhiliang Huang , Tingting Shi","doi":"10.1016/j.advms.2025.01.001","DOIUrl":"10.1016/j.advms.2025.01.001","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to evaluate the prognostic value of contrast-enhanced ultrasound (CEUS) combined with tumour markers in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA).</div></div><div><h3>Methods</h3><div>MWA patients with HCC were divided into good prognosis (n = 75) and poor prognosis (n = 69) groups. The levels of alpha-fetoprotein (AFP), carbohydrate antigen (CA19-9), and carcinoembryonic antigen (CEA) before and after MWA were analysed using an independent sample <em>t</em>-test. The correlation between prognosis, ablation lesion area, and tumour marker levels were analysed by Pearson's correlation. The diagnostic power of the ablation lesion area combined with tumour marker levels for the prognosis of patients with MWA was analysed using receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>The levels of AFP, CA19-9, and CEA in the good prognosis group were significantly lower than those in the poor prognosis group (all <em>P</em> < 0.001). The levels of all tumour markers were significantly negatively correlated with the prognosis of patients who underwent MWA (all r < 0, <em>P</em> < 0.001) and positively correlated with the area of tumour-ablated lesions (r > 0, <em>P</em> < 0.001). Moreover, the diagnostic efficacy of CEUS combined with tumour markers for the prognosis of patients who underwent MWA was significantly higher than that of either single diagnostic modality.</div></div><div><h3>Conclusions</h3><div>CEUS combined with tumour marker monitoring can effectively improve the accuracy of prognostic diagnosis in patients with MWA and provide a reference for timely and reasonable treatment and therapeutic evaluation.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 79-85"},"PeriodicalIF":2.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926237","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