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Yishen Huatan Huoxue decoction and quercetin ameliorate decidualization dysfunction in polycystic ovary syndrome: A comprehensive investigation combining clinical trial and experimental studies. 益神化瘀汤和槲皮素可改善多囊卵巢综合征的蜕膜功能障碍:一项结合临床试验和实验研究的综合调查
IF 3.1 Q1 Medicine Pub Date : 2024-06-06 Epub Date: 2024-04-19 DOI: 10.5582/ddt.2024.01003
Jing Wang, Lisha Li, Jing Zhou, Xinyao Pan, Qing Qi, Hongmei Sun, Ling Wang

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.

多囊卵巢综合征(PCOS)是一种常见的妇科内分泌疾病,发病机制复杂,治疗手段有限。益神化瘀汤作为一种传统中药配方,在治疗多囊卵巢综合征方面具有显著疗效。然而,益肝化瘀汤发挥治疗作用的具体机制仍不清楚。在本研究中,我们研究了玉竹和槲皮素对脱氢表雄酮诱导的多囊卵巢综合征小鼠的治疗作用,并考察了槲皮素在高胰岛素血症条件下对T-HESCs蜕膜化的影响。结果表明,YHHD能降低多囊卵巢综合征患者的早期流产率,并能显著改善多囊卵巢综合征小鼠的糖代谢紊乱、性激素水平和发情周期。槲皮素可减轻高胰岛素水平的影响,恢复T-HESCs中胰岛素受体底物1/2(IRS1/2)和葡萄糖转运体4(GLUT4)的低表达,这表明槲皮素可通过IRS1/2介导的GLUT4信号通路缓解高胰岛素诱导的蜕膜功能障碍。这项研究为YHHD提供了宝贵的分子见解,并凸显了槲皮素在治疗多囊卵巢综合征蜕膜功能障碍方面的治疗潜力。
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引用次数: 0
The prospects of automation in drug discovery research using silkworms. 利用家蚕进行药物发现研究的自动化前景。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-06 Epub Date: 2024-04-04 DOI: 10.5582/ddt.2024.01013
Atsushi Miyashita, Masanobu Miyauchi, Fumiaki Tabuchi

We have established several models of infectious diseases in silkworms to explore disease-causing mechanisms and identify new antimicrobial substances. These models involve injecting laboratory-cultured pathogens into silkworms and monitoring their survival over a period of days. The use of silkworms is advantageous because they are cost-effective and raise fewer ethical concerns than mammalian subjects, allowing for larger experimental group sizes. To capitalize on these benefits, there is a growing importance in mechanizing and automating the experimental processes that currently require manual labor. This paper discusses the future of laboratory automation, specifically through the mechanization and automation of silkworm-based experimental procedures.

我们建立了多个家蚕传染病模型,以探索致病机制和鉴定新的抗菌物质。这些模型包括将实验室培养的病原体注射到蚕体内,并在数天内监测其存活情况。使用蚕的优势在于成本效益高,而且与哺乳动物相比,蚕引起的伦理问题较少,因此实验组规模较大。为了充分利用这些优势,将目前需要手工劳动的实验过程机械化和自动化变得越来越重要。本文讨论了实验室自动化的未来,特别是通过以蚕为基础的实验程序的机械化和自动化。
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引用次数: 0
Beneficial impact of visual stimulation-based digital therapeutics on blood pressure control in non-hypertensive individuals. 基于视觉刺激的数字疗法对非高血压患者血压控制的有益影响。
IF 3.1 Q1 Medicine Pub Date : 2024-06-06 Epub Date: 2024-04-24 DOI: 10.5582/ddt.2024.01023
Yiwen Jiang, Hong Liu, Lingrui Yang, Chen Wu, Feng Jiang, Yaosheng Wang

Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.

高血压患者和非高血压患者都会发生与高血压相关的疾病。然而,迄今为止很少有研究探讨非高血压患者的血压控制问题。这项前后对比研究旨在探讨基于视觉刺激的数字疗法(VS-DTx)对血压和心率(HR)的影响。本研究共纳入了 83 名符合条件的非高血压患者。采用 McNemar 检验和配对样本 Wilcoxon Signed Rank 检验来评估对照阶段与干预阶段(使用 VS-DTx)之间血压和心率的下降率和差异。配对相关分析用于分析两个阶段之间的相关性。研究发现,VS-DTx 阶段的收缩压(SBP)和平均动脉压(MAP)呈下降趋势(66.2% vs 49.3%;68.7% vs 55.4%)。在 VS-DTx 阶段,平均 SBP 从 114.73 mm Hg 降至 111.18 mm Hg,平均 MAP 从 87.96 mm Hg 降至 84.88 mm Hg。成对样本 Wilcoxon 检验显示,ΔSBP(Z = -3.296;P < 0.01)和ΔMAP(Z = -2.386;P < 0.05)均存在差异(Δ定义为基线与刺激后的差异)。成对相关分析显示,VS-DTx 影响了浏览数字设备阶段和 VS-DTx 阶段的 MAP 降低(r = 0.33;P < 0.01)。结果表明,VS-DTx 可能对血压(包括 SBP 和 MAP)有一定的影响。本研究初步探讨了 VS-DTx 对血压可能产生的影响,为今后的数字血压管理研究提供了一些有益的启示。
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引用次数: 0
Evaluation of appropriateness of alerts overrides and physicians' responses of the medication-related clinical decision support system in China, a hospital-based study. 以医院为基础的研究:对中国用药相关临床决策支持系统的警报重设适当性和医生反应的评估。
IF 3.1 Q1 Medicine Pub Date : 2024-06-06 Epub Date: 2024-04-24 DOI: 10.5582/ddt.2024.01012
Li Jin, Huan Fang, Jie Shen, Zhigao He, Yi Li, Liang Dong, Jiali Feng, Tetsuya Asakawa

This study was designed to investigate the state quo of the appropriateness of alerts overrides of the medication-related clinical decision support system (MRCDSS) in China. The medication-related alerts in one hospital from Jan 2022 to Dec 2022 were acquired and sampled. Rates of alert overrides, appropriateness of alert generation and physicians' responses were observed. Total 14,612 medication-related alerts (≤ level 3) were recorded, of those, 12,659 (86.6%) alerts were overridden. The top 3 alert types were: drug and diagnosis contraindications (23.8%), drug and test value contraindications (23.3%), and compatibility issues (17.7%). Of all sampled 1,501 alerts, 80.2% of them were appropriately overridden by the physicians. The appropriate rate of alert generation was 57.9% and the inappropriate rate was 42.1%. The inappropriate rate of physicians' responses was 17.8%, and 2.0% physicians' responses were undetermined. A few medications accounted for over 10% of overrides, 88.3% of "overridden reasons" inputted by the physicians were meaningless characters or values, indicating an obvious "alert fatigue" in these physicians. Our results indicated that the overridden rate of MRCDSS in China was still high, and appropriateness of generation of alert was quite low. These data indicated that the MRCDSS currently using in China still needs constantly optimization and timely maintenance. Proper sensitivity to reduce triggering of useless alerts and generation of alert fatigue might play a vital role. We believed that these findings are helpful for better understanding the state quo of MRCDSS in China and providing useful insights for future developing and improving MRCDSS.

本研究旨在调查中国与用药相关的临床决策支持系统(MRCDSS)警报覆盖的适当性现状。研究获取并抽取了一家医院从 2022 年 1 月至 2022 年 12 月的用药相关警报。观察了警报覆盖率、警报生成的适当性和医生的反应。共记录了14,612个药物相关警报(≤3级),其中12,659个(86.6%)警报被覆盖。前 3 种警报类型是:药物和诊断禁忌(23.8%)、药物和检测值禁忌(23.3%)以及兼容性问题(17.7%)。在所有抽样的 1,501 个警报中,80.2% 的警报被医生适当地覆盖。警报生成的适当率为 57.9%,不适当率为 42.1%。医生回复的不恰当率为 17.8%,2.0% 的医生回复不确定。少数几种药物的超限率超过 10%,88.3% 的医生输入的 "超限原因 "是无意义的字符或数值,这表明这些医生存在明显的 "警报疲劳"。我们的研究结果表明,中国的 MRCDSS 超限率仍然很高,警报生成的适当性相当低。这些数据表明,中国目前使用的 MRCDSS 仍需不断优化和及时维护。适当的灵敏度对于减少无用警报的触发和警报疲劳的产生可能起到至关重要的作用。我们相信,这些发现有助于更好地了解中国 MRCDSS 的现状,并为今后开发和改进 MRCDSS 提供有益的启示。
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引用次数: 0
Rapamycin vs TORin-1 or Gleevec vs Nilotinib: Simple chemical evolution that converts PAK1-blockers to TOR-blockers or vice versa? 雷帕霉素与 TORin-1 或格列卫与尼罗替尼:将 PAK1 受体转换为 TOR 受体或反之亦然的简单化学进化?
IF 3.1 Q1 Medicine Pub Date : 2024-06-06 Epub Date: 2024-04-04 DOI: 10.5582/ddt.2023.01097
Hiroshi Maruta, Hong He

Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on "PAK1", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.

PAK1(RAC/CDC42 激活激酶 1)和 TOR(雷帕霉素靶蛋白)都是主要的致癌/老化激酶。然而,它们在我们的免疫系统中却扮演着相反的角色,即免疫系统受到 PAK1 的抑制,而需要 TOR。因此,PAK1 受体阻断剂比 TOR 受体阻断剂更能有效治疗癌症。自2015年我们从基因上发现PDGF诱导的黑色素生成依赖于 "PAK1 "以来,我们能够筛选出一系列PAK1受体阻断剂,作为黑色素生成抑制剂,最终促进长寿。有趣的是,雷帕霉素作为第一种TOR抑制剂能促进黑色素生成,这清楚地表明TOR抑制了黑色素生成。然而,一种名为 TORin-1 的新型 TOR 抑制剂不再抑制免疫系统,而且还能阻止细胞培养中的黑色素生成。这些观察结果有力地表明,TORin-1 在体内的作用是 PAK1 受体阻断剂,而不是 TOR 受体阻断剂。因此,细胞培养中的黑色素生成极有可能使我们能够区分 PAK1 受体阻断剂和 TOR 受体阻断剂。
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引用次数: 0
Metastasis to hypopharynx from epidermotropic metastatic malignant melanoma. 表皮转移性恶性黑色素瘤转移到下咽。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-06 Epub Date: 2024-04-17 DOI: 10.5582/ddt.2024.01017
Satoru Mizuhashi, Azusa Miyashita, Haruka Kuriyama, Toshihiro Kimura, Hisashi Kanemaru, Satoru Miyamaru, Sho Saeki, Satoshi Fukushima

Previous reports proposed the concept and criteria of epidermotropic metastatic malignant melanoma (EMMM): (a) dermal involvement equal to or broader than the epidermal involvement, (b) atypical melanocytes within the dermis, (c) thinning of the epidermis, (d) widening of the papillary dermis with an epithelial collarette, and (e) vascular invasion of atypical melanocytes. However, it remains unclear whether EMMM also involves the mucosal epithelium. In this case, the patient was diagnosed with EMMM based on the histopathological findings of the patient's multiple skin lesions and clinical course. The patient also developed metastasis to the hypopharynx. Although histopathological findings of the lesion suggested the possibility of melanoma in situ, as the lesion included atypical melanocytes in the mucosal epithelium, the clinical course supported the diagnosis of hypopharyngeal metastasis from EMMM. This case suggests that EMMM may have epitheliotropic features not only in the skin but also in the mucosa.

以往的报告提出了表皮转移性恶性黑色素瘤(EMMM)的概念和标准:(a) 真皮受累范围等于或大于表皮受累范围;(b) 真皮内有非典型黑色素细胞;(c) 表皮变薄;(d) 乳头状真皮增宽并伴有上皮环;(e) 非典型黑色素细胞的血管侵犯。然而,目前仍不清楚 EMMM 是否也会累及粘膜上皮。在本病例中,根据患者多处皮肤病变的组织病理学结果和临床病程,患者被诊断为 EMMM。患者还出现了下咽转移。虽然病变的组织病理结果表明可能是原位黑色素瘤,因为病变包括粘膜上皮中的非典型黑色素细胞,但临床病程支持 EMMM 下咽转移的诊断。本病例表明,EMMM不仅在皮肤上,而且在粘膜上也可能具有上皮性特征。
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引用次数: 0
Association between the experience of exertional heat illness (EHI) and living conditions of collegiate student athletes. 大学生运动员的劳累性热病(EHI)经历与生活条件之间的关系。
IF 3.1 Q1 Medicine Pub Date : 2024-03-20 Epub Date: 2024-02-15 DOI: 10.5582/ddt.2023.01094
Yoko Iio, Mamoru Tanaka, Hana Kozai, Yuka Aoyama, Yukihiro Mori, Manato Seguchi, Morihiro Ito

Exertional heatstroke (EHS), a severe form of exertional heat illness (EHI), is the third leading cause of death in athletes; thus, early detection and prevention of EHI can help prevent EHS, which is a life-threatening condition. This study aimed to clarify the association between the cognizance of experiencing EHI and living conditions and specific EHI symptoms among collegiate athletes. This study was conducted in October 2022 by administering a questionnaire to 237 male collegiate athletes. Of the 215 (90.7%) respondents, 197 (91.6%) provided valid responses; among them, 88 (44.7%) responded they had experienced EHI, while 109 (55.3%) had not. A history of medical examinations due to EHI, having experienced headaches during summer activities, and having read the EHI manual were factors indicating cognizance of EHI. The number of times meals containing a staple food, main dish, and side dish were eaten in a day was a factor in preventing EHI. Early detection of EHI is important for its prevention, and it is important that athletes themselves have knowledge of symptoms and can correctly self-diagnose EHI. Emphasizing the potential of a well-balanced dietary intake has the potential to prevent EHI is crucial.

劳累性中暑(EHS)是劳累性热病(EHI)的一种严重形式,是导致运动员死亡的第三大原因;因此,及早发现和预防劳累性热病有助于防止危及生命的劳累性中暑。本研究旨在阐明大学生运动员对经历 EHI 的认知和生活条件与特定 EHI 症状之间的关联。本研究于 2022 年 10 月进行,向 237 名男性大学生运动员发放了调查问卷。在 215 名(90.7%)受访者中,197 名(91.6%)提供了有效回答;其中 88 名(44.7%)回答曾经历过 EHI,109 名(55.3%)没有经历过。曾因胃肠道感染而进行过体检、在夏季活动中出现过头痛、阅读过胃肠道感染手册等因素表明他们对胃肠道感染有所认识。一天中吃主食、主菜和配菜的次数是预防 EHI 的一个因素。及早发现 EHI 对预防 EHI 非常重要,运动员自身对 EHI 的症状有所了解并能正确进行自我诊断也很重要。强调均衡膳食对预防 EHI 的潜在作用至关重要。
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引用次数: 0
Usefulness of a new immunochromatographic assay using fluorescent silica nanoparticles for serodiagnosis of Thai patients with amebiasis. 使用荧光硅纳米粒子的新型免疫层析检测法在泰国阿米巴病患者血清诊断中的实用性。
IF 3.1 Q1 Medicine Pub Date : 2024-03-20 Epub Date: 2024-02-15 DOI: 10.5582/ddt.2023.01102
Azumi Kakino, Urassaya Pattanawong, Napaporn Kuamsab, Tatsuya Imai, Chaturong Putaporntip, Satomi Asai, Xunjia Cheng, Somchai Jongwutiwes, Hiroshi Tachibana

A fluorescence immunochromatography (FIC) kit was developed recently using fluorescent silica nanoparticles coated with a recombinant C-terminal fragment of the surface lectin intermediate subunit (C-Igl) of Entamoeba histolytica to establish rapid serodiagnosis of amebiasis. We further evaluated the system using serum samples from 52 Thai patients with amebiasis. Of the patients, 50 (96%) tested positive using FIC. The samples were also tested using enzyme-linked immunosorbent assay (ELISA) with C-Igl as the antigen. Two samples were negative on ELISA but positive on FIC. The correlation coefficient between the fluorescence intensity using FIC and the optical density value using ELISA was 0.5390, indicating a moderate correlation between the two tests. Serum samples from 20 patients with malaria and 22 patients with Clostridioides difficile infection were also tested using FIC. The false-positive rates were 4/20 (20%) and 1/22 (4%) in patients with malaria and C. difficile infection, respectively. Combining the data from the present study with our previous study, the sensitivity and specificity of FIC were determined to be 98.5% and 95.2%, respectively. The results of the 50 samples were studied using a fluorescence scope and a fluorescence intensity reader, and the findings were compared. Disagreements were found in only two samples showing near-borderline fluorescence intensity, indicating that the use of scope was adequate for judging the results. These results demonstrate that FIC is a simple and rapid test for the serodiagnosis of amebiasis.

最近,我们开发了一种荧光免疫层析(FIC)试剂盒,该试剂盒使用了涂有恩塔莫阿米巴组织溶解虫表面凝集素中间亚基(C-Igl)重组 C 端片段的荧光硅纳米粒子,可用于阿米巴病的快速血清诊断。我们使用 52 名泰国阿米巴病患者的血清样本对该系统进行了进一步评估。其中 50 名患者(96%)的 FIC 检测结果呈阳性。我们还使用以 C-Igl 为抗原的酶联免疫吸附试验(ELISA)对样本进行了检测。有两个样本在 ELISA 检测中呈阴性,但在 FIC 检测中呈阳性。使用 FIC 检测的荧光强度与使用 ELISA 检测的光密度值之间的相关系数为 0.5390,表明这两种检测方法之间存在中度相关性。20 名疟疾患者和 22 名艰难梭菌感染患者的血清样本也用 FIC 进行了检测。疟疾和艰难梭菌感染患者的假阳性率分别为 4/20(20%)和 1/22 (4%)。结合本研究和我们之前的研究数据,FIC 的灵敏度和特异度分别为 98.5% 和 95.2%。使用荧光显微镜和荧光强度阅读器对 50 份样本的结果进行了研究和比较。结果发现,只有两个样本的荧光强度接近边界线,表明使用荧光显微镜足以判断结果。这些结果表明,FIC 是一种用于阿米巴病血清诊断的简单而快速的检测方法。
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引用次数: 0
Inhibitory effects of kaempferol, quercetin and luteolin on the replication of human parainfluenza virus type 2 in vitro. 山奈酚、槲皮素和木犀草素对人副流感病毒 2 型体外复制的抑制作用。
IF 3.1 Q1 Medicine Pub Date : 2024-03-20 Epub Date: 2024-02-20 DOI: 10.5582/ddt.2023.01099
Kae Sakai-Sugino, Jun Uematsu, Hidetaka Yamamoto, Sahoko Kihira, Mitsuo Kawano, Miwako Nishio, Masato Tsurudome, Hidehisa Sekijima, Myles O'Brien, Hiroshi Komada

The eight flavonoids, apigenin, chrysin, hesperidin, kaempferol, myricetin, quercetin, rutin and luteolin were tested for the inhibition of human parainfluenza virus type 2 (hPIV-2) replication. Three flavonoids out of the eight, kaempferol, quercetin and luteolin inhibited hPIV-2 replication. Kaempferol reduced the virus release (below 1/10,000), partly inhibited genome and mRNA syntheses, but protein synthesis was observed. It partly inhibited virus entry into the cells and virus spreading, and also partly disrupted microtubules and actin microfilaments, indicating that the virus release inhibition was partly caused by the disruption of cytoskeleton. Quercetine reduced the virus release (below 1/10,000), partly inhibited genome, mRNA and protein syntheses. It partly inhibited virus entry and spreading, and also partly destroyed microtubules and microfilaments. Luteolin reduced the virus release (below 1/100,000), largely inhibited genome, mRNA and protein syntheses. It inhibited virus entry and spreading. It disrupted microtubules and microfilaments. These results indicated that luteolin has the most inhibitory effect on hPIV-2 relication. In conclusion, the three flavonoids inhibited virus replication by the inhibition of genome, mRNA and protein syntheses, and in addition to those, by the disruption of cytoskeleton in vitro.

对芹菜素、菊黄素、橙皮甙、山奈酚、杨梅素、槲皮素、芦丁和木犀草素这八种黄酮类化合物进行了抑制人副流感病毒 2 型(hPIV-2)复制的测试。在八种黄酮类化合物中,山奈酚、槲皮素和木犀草素这三种黄酮类化合物抑制了 hPIV-2 的复制。山奈酚减少了病毒的释放(低于 1/10,000),部分抑制了基因组和 mRNA 的合成,但观察到了蛋白质的合成。山奈酚部分抑制了病毒进入细胞和病毒扩散,还部分破坏了微管和肌动蛋白微丝,表明病毒释放抑制部分是由细胞骨架破坏引起的。槲皮素减少了病毒的释放(低于 1/10,000),部分抑制了基因组、mRNA 和蛋白质的合成。它部分抑制了病毒的进入和扩散,还部分破坏了微管和微丝。叶黄素可减少病毒释放(低于 1/100,000),在很大程度上抑制基因组、mRNA 和蛋白质的合成。它抑制了病毒的进入和扩散。它还能破坏微管和微丝。这些结果表明,木犀草素对 hPIV-2 复制的抑制作用最强。总之,这三种黄酮类化合物通过抑制基因组、mRNA和蛋白质的合成来抑制病毒复制,此外还通过破坏细胞骨架来抑制病毒复制。
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引用次数: 0
PD-1/PD-L1 inhibitors associated hypophysitis: An analysis from the FAERS database and case reports. 与 PD-1/PD-L1 抑制剂相关的肾上腺皮质功能减退症:来自 FAERS 数据库和病例报告的分析。
IF 3.1 Q1 Medicine Pub Date : 2024-03-20 Epub Date: 2024-02-20 DOI: 10.5582/ddt.2023.01092
Shanshan Chen, Linqi Ouyang, Lian Li, Yuyang Xiao, Shengfeng Wang

To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.

为了全面了解 PD-1/L1 抑制剂相关性肾上腺皮质功能减退症(PD-1/L1-irH),我们结合使用了反比分析法和病例分析法来全面描述 PD-1/L1-irH 的临床特征。在 FAERS(FDA 不良事件报告系统)中,所有 PD-1/PD-L1 抑制剂都出现了明显的肾上腺皮质功能减退症信号。FAERS 和病例分析均显示,PD-1/L1-irH 更常见于男性、PD-1 抑制剂使用者和 65 岁以上的患者。FAERS 中的中位发病时间为 101 天,病例分析中的中位发病时间为 8 个周期。在病例分析中,即使在停药数月(4-15 个月)后,仍有 8 例晚期 PD-1/L1-irH 发病。正如 FAERS 所显示的,PD-1/L1-irH 的预后往往不佳,一般导致 64.66% 的患者住院,12.59% 的患者死亡。对 84 例病例的分析显示,疲劳是 PD-1/L1-irH 最突出的症状,其次是厌食、低钠血症和低血压。同时,孤立的促肾上腺皮质激素(ACTH)缺乏症在PD-1/L1-irH中尤为普遍(85.71%),而性腺激素或垂体后叶激素缺乏症则很少见。几乎所有病例(81/84)都使用了糖皮质激素,61.9%的病例使用了生理剂量或应激剂量,26.2%的病例使用了大剂量。大多数病例(58.3%)在确诊PD-1/L1-irH前已出现良好的肿瘤反应。即使停药后,PD-1/L1-irH 也可能在整个治疗期间出现。临床医生应更加关注PD-1抑制剂使用者、男性和老年患者。PD-1/L1-irH有可能危及生命,因此早期诊断和及时治疗至关重要。
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Drug Discoveries and Therapeutics
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