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Diagnostic Accuracy of Transthoracic Echocardiography for Acute Type A Aortic Syndrome: A Systematic Review and Meta-Analysis. 经胸超声心动图对急性 A 型主动脉综合征的诊断准确性:系统回顾与元分析》。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-05-10 DOI: 10.1016/j.bj.2024.100747
Hsin-Tzu Yeh, Sz-Wei Lu, Tzu-Heng Cheng, Jian-Xun Lu, Chien-Han Hsiao, Chieh-Ching Yen

Background: Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS.

Methods: We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio [1], and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria.

Results: Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38-76%) and 94% (95% CI, 89-97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85-94%) and 74% (95% CI, 61-84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)] in four studies.

Conclusions: Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.

背景:经胸超声心动图(TTE)目前被认为是疑似急性 A 型主动脉综合征(AAAS)患者的潜在一线成像检查。如果两个主动脉管腔之间有内膜瓣分隔,或在升主动脉看到主动脉壁增厚,则检测 AAAS 的直接 TTE 征象为阳性。间接 TTE 征象显示 AAAS 的高风险特征,如主动脉根部扩张、心包积液和主动脉瓣反流。我们的目的是总结有关 TTE 诊断准确性的现有临床证据,并评估其在疑似 AAAS 患者管理中的潜在作用:我们从 PubMed、EMBASE、MEDLINE 和 Cochrane 图书馆等数据库中纳入了以任何语言撰写的前瞻性或回顾性诊断队列研究,这些研究特别关注使用 TTE 诊断 AAAS。我们计算了 TTE 诊断 AAAS 的集合敏感性、特异性、阳性似然比 (PLR)、阴性似然比 (NLR)、诊断几率比 [1] 和分层汇总接收者操作特征曲线 (HSROC)。我们应用了诊断准确性质量评估(QUADAS-2)工具和推荐、评估、发展和评价分级(GRADE)质量评估标准:10项研究(2886名患者)被纳入荟萃分析。直接 TTE 征兆的汇总灵敏度和特异性分别为 58%(95% CI,38-76%)和 94%(95% CI,89-97%)。对于任何 TTE 征象,汇总的敏感性和特异性分别为 91%(95% CI,85-94%)和 74%(95% CI,61-84%)。四项研究的 HSROC 曲线下面积[0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)]显示,直接 TTE 征象的诊断准确性明显高于任何 TTE 征象:我们的研究表明,TTE 可作为疑似 AAAS 患者的初始影像学检查。鉴于其特异性较高,出现直接的 TTE 征象可能预示着 AAAS 的存在,而没有任何 TTE 征象,再加上临床怀疑度较低,则表明 AAAS 的可能性较低。
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引用次数: 0
Charting new territory: The Plasmodium falciparum tRNA modification landscape. 开拓新领域:恶性疟原虫 tRNA 修饰景观。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-05-09 DOI: 10.1016/j.bj.2024.100745
Benjamin Sian Teck Lee, Ameya Sinha, Peter Dedon, Peter Preiser

Ribonucleoside modifications comprising the epitranscriptome are present in all organisms and all forms of RNA, including mRNA, rRNA and tRNA, the three major RNA components of the translational machinery. Of these, tRNA is the most heavily modified and the tRNA epitranscriptome has the greatest diversity of modifications. In addition to their roles in tRNA biogenesis, quality control, structure, cleavage, and codon recognition, tRNA modifications have been shown to regulate gene expression post-transcriptionally in prokaryotes and eukaryotes, including humans. However, studies investigating the impact of tRNA modifications on gene expression in the malaria parasite Plasmodium falciparum are currently scarce. Current evidence shows that the parasite has a limited capacity for transcriptional control, which points to a heavier reliance on strategies for posttranscriptional regulation such as tRNA epitranscriptome reprogramming. This review addresses the known functions of tRNA modifications in the biology of P. falciparum while highlighting the potential therapeutic opportunities and the value of using P. falciparum as a model organism for addressing several open questions related to the tRNA epitranscriptome.

构成表转录组的核糖核苷修饰存在于所有生物体和所有形式的 RNA 中,包括 mRNA、rRNA 和 tRNA,它们是翻译机制的三大 RNA 组成部分。其中,tRNA 的修饰程度最高,tRNA 表转录组的修饰多样性也最大。除了在 tRNA 的生物发生、质量控制、结构、裂解和密码子识别等方面发挥作用外,tRNA 修饰还被证明可在原核生物和真核生物(包括人类)中转录后调控基因表达。然而,目前很少有研究调查 tRNA 修饰对恶性疟原虫基因表达的影响。目前的证据表明,寄生虫的转录调控能力有限,因此更依赖于转录后调控策略,如 tRNA 表转录组的重编程。本综述探讨了 tRNA 修饰在恶性疟原虫生物学中的已知功能,同时强调了潜在的治疗机会,以及将恶性疟原虫作为模式生物来解决与 tRNA 表转录组相关的几个未决问题的价值。
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引用次数: 0
"Mpox in MSM: Tackling Stigma, Minimizing Risk Factors, Exploring Pathogenesis, and Treatment Approaches". "男男性行为者中的 Mpox:消除耻辱感、尽量减少风险因素、探索发病机制和治疗方法"。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-05-09 DOI: 10.1016/j.bj.2024.100746
Arpan Acharya, Narendra Kumar, Kamal Singh, Siddappa N Byrareddy

Mpox is a zoonotic disease caused by the monkeypox virus (MPV), primarily found in Central and West African countries. The typical presentation of the disease before the 2022 mpox outbreak includes a febrile prodrome 5-13 days post-exposure, accompanied by lymphadenopathy, malaise, headache, and muscle aches. Unexpectedly, during the 2022 outbreak, several cases of atypical presentations of the disease were reported, such as the absence of prodromal symptoms and the presence of genital skin lesions suggestive of sexual transmission. As per the World Health Organization (WHO), as of March 20, 2024, 94,707 cases of mpox were reported worldwide, resulting in 181 deaths (22 in African endemic regions and 159 in non-endemic countries). The United States Centers for Disease Control and Prevention (CDC) reports a total of 32,063 cases (33.85% of total cases globally), with 58 deaths (32.04% of global deaths) due to mpox. Person-to-person transmission of mpox can occur through respiratory droplets and sustained close contact. However, during the 2022 outbreak of mpox, a high incidence of anal and perianal lesions among MSMs indicated sexual transmission of MPV as a major route of transmission. Since MSMs are disproportionately at risk for HIV transmission, this review discusses the risk factors, transmission patterns, pathogenesis, vaccine, and treatment options for mpox among MSM and people living with HIV (PLWH). Furthermore, we provide a brief perspective on the evolution of the MPV in immunocompromised people like PLWH.

猴痘是一种由猴痘病毒(MPV)引起的人畜共患疾病,主要出现在中非和西非国家。在 2022 年猴痘疫情爆发前,该病的典型表现包括接触后 5-13 天的发热前驱症状,并伴有淋巴结病、乏力、头痛和肌肉酸痛。意想不到的是,在 2022 年疫情爆发期间,报告了几例非典型表现的病例,如无前驱症状和出现生殖器皮损提示性传播。据世界卫生组织(WHO)统计,截至 2024 年 3 月 20 日,全球共报告 94 707 例麻风腮病例,造成 181 人死亡(非洲流行地区 22 人,非流行国家 159 人)。美国疾病控制和预防中心(CDC)报告的天花病例总数为 32063 例(占全球病例总数的 33.85%),死亡 58 例(占全球死亡人数的 32.04%)。天花可通过呼吸道飞沫和持续密切接触进行人际传播。然而,在 2022 年爆发的天花疫情中,男男性行为者肛门和肛周病变的高发病率表明,MPV 的性传播是主要传播途径。由于男男性行为者感染艾滋病毒的风险过高,本综述将讨论男男性行为者和艾滋病毒感染者(PLWH)感染痘病的风险因素、传播模式、发病机制、疫苗和治疗方案。此外,我们还从一个简短的角度探讨了 MPV 在艾滋病毒感染者等免疫力低下人群中的演变。
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引用次数: 0
Molecular Diagnosis of Nasopharyngeal Carcinoma: Past and Future 鼻咽癌的分子诊断:过去与未来
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1016/j.bj.2024.100748
Cheng-Lung Hsu, Yu-Sun Chang, Hsin-Pai Li
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引用次数: 0
ECG-surv: A deep learning-based model to predict time to 1-year mortality from 12-lead electrocardiogram. ECG-surv:基于深度学习的模型,通过 12 导联心电图预测 1 年死亡时间。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-30 DOI: 10.1016/j.bj.2024.100732
Ching-Heng Lin, Zhi-Yong Liu, Jung-Sheng Chen, Yang C Fann, Ming-Shien Wen, Chang-Fu Kuo

Background: Electrocardiogram (ECG) abnormalities have demonstrated potential as prognostic indicators of patient survival. However, the traditional statistical approach is constrained by structured data input, limiting its ability to fully leverage the predictive value of ECG data in prognostic modeling.

Methods: This study aims to introduce and evaluate a deep-learning model to simultaneously handle censored data and unstructured ECG data for survival analysis. We herein introduce a novel deep neural network called ECG-surv, which includes a feature extraction neural network and a time-to-event analysis neural network. The proposed model is specifically designed to predict the time to 1-year mortality by extracting and analyzing unique features from 12-lead ECG data. ECG-surv was evaluated using both an independent test set and an external set, which were collected using different ECG devices.

Results: The performance of ECG-surv surpassed that of the Cox proportional model, which included demographics and ECG waveform parameters, in predicting 1-year all-cause mortality, with a significantly higher concordance index (C-index) in ECG-surv than in the Cox model using both the independent test set (0.860 [95% CI: 0.859- 0.861] vs. 0.796 [95% CI: 0.791- 0.800]) and the external test set (0.813 [95% CI: 0.807- 0.814] vs. 0.764 [95% CI: 0.755- 0.770]). ECG-surv also demonstrated exceptional predictive ability for cardiovascular death (C-index of 0.891 [95% CI: 0.890- 0.893]), outperforming the Framingham risk Cox model (C-index of 0.734 [95% CI: 0.715-0.752]).

Conclusion: ECG-surv effectively utilized unstructured ECG data in a survival analysis. It outperformed traditional statistical approaches in predicting 1-year all-cause mortality and cardiovascular death, which makes it a valuable tool for predicting patient survival.

背景:心电图(ECG)异常已被证明具有作为患者生存预后指标的潜力。然而,传统的统计方法受到结构化数据输入的限制,无法充分利用心电图数据在预后建模中的预测价值:本研究旨在引入并评估一种深度学习模型,该模型可同时处理删减数据和非结构化心电图数据,用于生存分析。我们在此介绍一种名为 ECG-surv 的新型深度神经网络,它包括一个特征提取神经网络和一个时间到事件分析神经网络。该模型专门设计用于通过提取和分析 12 导联心电图数据中的独特特征来预测 1 年死亡率。使用独立测试集和外部集对 ECG-surv 进行了评估,这些测试集是使用不同的心电图设备收集的:结果:在预测 1 年全因死亡率方面,ECG-surv 的性能超过了包含人口统计学和心电图波形参数的 Cox 比例模型,在使用独立测试集时,ECG-surv 的一致性指数(C-index)明显高于 Cox 模型(0.860 [95% CI: 0.859- 0.861] vs. 0.796 [95% CI: 0.791- 0.800])和外部测试集(0.813 [95% CI: 0.807- 0.814] vs. 0.764 [95% CI: 0.755- 0.770])。ECG-surv对心血管死亡的预测能力(C指数为0.891 [95% CI:0.890- 0.893])也非常出色,优于Framingham风险Cox模型(C指数为0.734 [95% CI:0.715-0.752]):ECG-surv在生存分析中有效地利用了非结构化心电图数据。结论:ECG-surv 在生存分析中有效地利用了非结构化心电图数据,在预测 1 年全因死亡率和心血管死亡方面优于传统的统计方法,是预测患者生存的重要工具。
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引用次数: 0
Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway. 蚂蚁肉桂提取物通过抑制mTOR途径减轻博莱霉素诱导的小鼠肺纤维化。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100720
Ying-Wei Lan, Chia-En Chen, Tsung-Teng Huang, Tse-Hung Huang, Chuan-Mu Chen, Kowit-Yu Chong

Background: Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis.

Methods: The TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined.

Results: The A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa.

Conclusions: The Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

背景:肺纤维化是一种进行性弥漫性肺实质疾病,死亡率很高。研究表明,损伤的肺组织会释放各种促炎因子,并产生大量一氧化氮。此外,胶原蛋白的积累和氧化应激引起的损伤共同导致了肺纤维化。肉桂蕨是台湾特有的真菌,其发酵提取物具有抗炎作用,可减轻肝损伤。因此,我们假设并测试了使用肉桂提取物治疗肺纤维化的可行性:方法:采用TGF-β1诱导的人肺成纤维细胞(MRC-5)体外细胞试验,评估肉桂提取物对MRC-5胶原蛋白生成的影响。对 8 周大的 ICR 小鼠气管内注射博莱霉素,然后在注射博莱霉素后的第 3 天喂食肉桂萃取物。在使用博莱霉素后第 21 天,检测肺功能测试、肺组织中炎症和纤维化相关基因的表达水平以及组织病理学变化:结果:肉桂提取物能显著降低TGF-β1诱导的MRC-5细胞中胶原蛋白的表达水平。肉桂提取物治疗博莱霉素诱导的肺纤维化小鼠体重增加,肺功能改善,肺组织炎症因子和纤维化指标表达水平降低,组织病理学结果显示肺泡间质增厚减轻:结论:肉桂酸蚂蚁提取物能显著保护小鼠免受博莱霉素诱导的肺损伤,改善小鼠的体重增加和肺功能,减少炎症和纤维化指标的表达。
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引用次数: 0
Pharmaceutical cost savings from the treatment of oncology patients in clinical trials. 临床试验中治疗肿瘤患者节省的医药成本。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100742
Borja Gómez Mediavilla, Paloma Lanza León, Virginia Martínez Callejo, David Cantarero Prieto, María Lanza Postigo, Matilde Salcedo Lambea, Yolanda Blanco Mesonero, María Ochagavia Sufrategui, Ignacio Durán, Carmen María Sarabia Cobo

Objective: The aim of this study was twofold: to assess the annual pharmaceutical savings associated with the treatment of cancer patients at Marqués de Valdecilla University Hospital and to estimate the cost of innovative antineoplastic therapies that patients receive as experimental treatment, both during clinical trials throughout 2020.

Material and methods: An observational and financial analysis of the drug cost related to clinical trials was applied. Direct cost savings to the Regional Health System of Cantabria and the cost of innovative therapies used as an experimental treatment in clinical trials were quantified.

Results: This study includes 38 clinical trials with a sample of 101 patients. The clinical trials analyzed provide a total cost savings of €603,350.21 and an average cost saving of €6,630.22 per patient. Furthermore, the total investment amounts to €789,892.67, with an average investment of €15,488.09 per patient.

Conclusions: Clinical trials are essential for the advancement of science. Furthermore, clinical trials can be a significant source of income for both hospitals and Regional Health Systems, contributing to their financial sustainability.

目的:这项研究有两个目的:评估巴尔德西亚侯爵大学医院每年在治疗癌症患者方面节省的药品费用;估算患者在 2020 年临床试验期间作为试验性治疗接受创新抗肿瘤疗法的费用:对与临床试验相关的药物成本进行了观察和财务分析。对坎塔布里亚地区卫生系统直接节省的费用和临床试验中作为试验性治疗的创新疗法的费用进行了量化:这项研究包括38项临床试验,样本为101名患者。所分析的临床试验共节约成本603,350.21欧元,平均每位患者节约成本6,630.22欧元。此外,总投资额为 789,892.67 欧元,每位患者平均投资额为 15,488.09 欧元:临床试验对科学进步至关重要。此外,临床试验还是医院和地区医疗系统的重要收入来源,有助于其财务可持续性。
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引用次数: 0
Applications of Deep Learning in Trauma Radiology: A Narrative Review. 深度学习在创伤放射学中的应用:叙述性综述。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100743
Chi-Tung Cheng, Chun-Hsiang Ooyang, Shih-Ching Kang, Chien-Hung Liao

Diagnostic imaging is essential in modern trauma care for initial evaluation and identifying injuries requiring intervention. Deep learning (DL) has become mainstream in medical image analysis and has shown promising efficacy for classification, segmentation, and lesion detection. This narrative review provides the fundamental concepts for developing DL algorithms in trauma imaging and presents an overview of current progress in each modality. DL has been applied to detect free fluid on Focused Assessment with Sonography for Trauma (FAST), traumatic findings on chest and pelvic X-rays, and computed tomography (CT) scans, identify intracranial hemorrhage on head CT, detect vertebral fractures, and identify injuries to organs like the spleen, liver, and lungs on abdominal and chest CT. Future directions involve expanding dataset size and diversity through federated learning, enhancing model explainability and transparency to build clinician trust, and integrating multimodal data to provide more meaningful insights into traumatic injuries. Though some commercial artificial intelligence products are Food and Drug Administration-approved for clinical use in the trauma field, adoption remains limited, highlighting the need for multi-disciplinary teams to engineer practical, real-world solutions. Overall, DL shows immense potential to improve the efficiency and accuracy of trauma imaging, but thoughtful development and validation are critical to ensure these technologies positively impact patient care.

在现代创伤护理中,诊断成像对于初步评估和识别需要干预的损伤至关重要。深度学习(DL)已成为医学图像分析的主流,并在分类、分割和病变检测方面显示出良好的效果。这篇叙述性综述提供了在创伤成像中开发深度学习算法的基本概念,并概述了每种模式的当前进展。DL 已被用于检测创伤超声聚焦评估 (FAST) 中的游离液体、胸部和骨盆 X 光片以及计算机断层扫描 (CT) 扫描中的创伤发现、头部 CT 中的颅内出血、脊椎骨折检测,以及腹部和胸部 CT 中脾脏、肝脏和肺脏等器官的损伤。未来的发展方向包括:通过联合学习扩大数据集的规模和多样性;提高模型的可解释性和透明度,以建立临床医生的信任;整合多模态数据,为创伤性损伤提供更有意义的见解。尽管一些商业人工智能产品已获得食品药品管理局的批准,可用于创伤领域的临床应用,但其应用仍然有限,这凸显了多学科团队设计实用、真实世界解决方案的必要性。总体而言,DL 在提高创伤成像的效率和准确性方面显示出巨大的潜力,但要确保这些技术对患者护理产生积极影响,深思熟虑的开发和验证至关重要。
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引用次数: 0
The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer. 黄芪多糖对T细胞和巨噬细胞抑制前列腺癌的作用和机制
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-25 DOI: 10.1016/j.bj.2024.100741
Ching-Yuan Wu, Yao-Hsu Yang, Yu-Shih Lin, Li-Hsin Shu, Hung-Te Liu, Chung-Kuang Lu, Yu-Huei Wu, Yu-Heng Wu

Background: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated.

Methods: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays.

Results: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells.

Conclusion: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

背景:黄芪多糖(APS)对前列腺癌的影响及其内在机制,尤其是其在免疫调节中的作用,仍未得到充分阐明:本研究采用 XTT 法评估前列腺癌细胞和巨噬细胞的增殖情况。T细胞增殖采用羧基荧光素二乙酸琥珀酰亚胺酯标记法进行测定。通过流式细胞术、Western 印迹分析、酶联免疫吸附试验、定量 PCR 和细胞因子膜阵列,仔细研究了 APS 对 T 细胞和巨噬细胞的影响。通过 PD-L1/PD-1 均匀试验研究了 APS 对 PD-L1 和 PD-1 之间相互作用的影响。此外,还通过迁移试验探讨了 T 细胞和巨噬细胞的条件培养基对 PC-3 细胞迁移的影响:结果:观察发现,浓度为 1 毫克/毫升和 5 毫克/毫升的 APS 可增强 CD8+ T 细胞的增殖。浓度为 5 毫克/毫升时,APS 可激活 CD4+ 和 CD8+ T 细胞,减轻受γ干扰素(IFN-γ)或奥沙利铂刺激的前列腺癌细胞中 PD-L1 的表达,并适度减少 PD-1+ CD4+ 和 PD-1+ CD8+ T 细胞的数量。此外,该浓度的APS还阻碍了PD-L1和PD-1之间的相互作用,抑制了由RAW 264.7细胞、THP-1细胞、CD4+ T细胞和CD8+ T细胞介导的前列腺癌迁移的促进作用,并启动了经APS(5 mg/mL)处理的CD8+ T细胞、RAW 264.7细胞或THP-1细胞的条件培养基处理的前列腺癌细胞的凋亡:研究结果表明,5 mg/mL APS 在调节 PD-1/PD-L1 通路和影响免疫反应(包括 T 细胞和巨噬细胞)方面具有潜在作用。因此,建议进一步开展体内研究,以评估 APS 的疗效。
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引用次数: 0
Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice. 桂枝茯苓丸可改善小鼠由金刚烷胺 A 引起的自身免疫性肝炎。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2024-04-25 DOI: 10.1016/j.bj.2024.100731
Shun-Li Kuo, Chun-Han Su, Kuei-Hung Lai, Yu-Chia Chang, Jyh-Sheng You, Hsin-Hsin Peng, Chun-Hong Chen, Chi-Chen Lin, Po-Jen Chen, Tsong-Long Hwan

Background: Autoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH.

Methods: The tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined.

Results: Oral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice.

Conclusions: Our findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.

背景:自身免疫性肝炎(AIH)是一种免疫介导的肝病,伴有严重的并发症。自身免疫性肝炎多见于女性,需要有效的药物来治疗。桂枝茯苓丸(GZFLW)是一种用于治疗各种妇科疾病的传统中药配方。本研究旨在拓展桂枝茯苓丸治疗 AIH 的新用途:方法:采用串联质谱分析法鉴定 GZFLW 中的次生代谢物。方法:采用串联质谱分析法鉴定了 GZFLW 中的次生代谢物,并在小鼠由 Con A 诱导的 AIH 模型中测试了 GZFLW 的治疗效果。确定了抗细胞凋亡、抗氧化和免疫调节保护作用的民族药理学机制:结果:在 Con A 诱导的体内肝毒性模型中,口服 GZFLW 可减轻 AIH。基于串联质谱的分析确定了 GZFLW 中的 15 种次生代谢物。GZFLW 能显著缓解 Con A 诱导的 AIH 综合征,包括肝细胞凋亡、炎症、活性氧积累、功能衰竭和死亡。从机理上讲,GZFLW抑制了Caspase依赖性细胞凋亡,恢复了抗氧化系统,并减少了Con A处理小鼠肝脏中促炎细胞因子的产生。此外,GZFLW还能抑制Con A诱导的小鼠肝脏炎症细胞浸润、脾脏T细胞活化和脾肿大:我们的研究结果证明了 GZFLW 在治疗 AIH 方面的应用潜力。结论:我们的研究结果表明了 GZFLW 在治疗 AIH 方面的应用潜力,这也促使我们进一步研究 GZFLW 作为 AIH 及其他肝病治疗方法的可能性。
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