本研究不涉及伦理批准和参与同意。本研究中使用的数据来自基因数据库。
1. 疾病靶点预测
<ol><li>访问 GeneCards 数据库 （https://www.genecards.org） 和在线孟德尔遗传人类数据库 （OMIM， https://www.omim.org），使用“肛门湿疹”作为疾病靶点的搜索词。</li>
	<li>下载疾病目标的电子表格。删除重复目标，获取肛门湿疹目标。</li>
</ol>2.活性成分的选择
<ol><li>在中医药系统药理学数据库（TCMSP;http://tcmspw.com/tcmsp.php）上搜索关键词“靛蓝、金柏、煅烧石膏、炉甘石和中国瘿”，即可获得SDG的候选活性成分和靶点清单。</li>
	<li>将该组分委托给瑞士ADME数据库（http://www.swissadme.ch/index.php），提取那些表现出“高”GI吸收的成分的详细信息，并至少有两个“是”DL值作为活性元素。 注意：通常，只有数据库中类药物 （DL） 值 ≥0.18 的成分才作为活性成分包含在内。</li>
</ol>3. PPI网络的构建和核心蛋白的筛选
<ol><li>在Venny2.1（https://bioinfogp.cnb.csic.es/tools/venny/index.html）中，将SDG和肛门湿疹的目标分别输入到LIST1和LIST2中。交叉点的视觉表示会立即生成。单击共享区域以显示“结果 ”部分中的常见目标。</li>
	<li>访问 STRING 数据库 （https://string-db.org/）。在“名称列表 ”字段中输入目标。然后选择 “智人 ”作为 “有机体 ”，并继续 “搜索”>“继续”。</li>
	<li>当结果可用时，打开 “高级设置” 并选择隐藏网络中断开连接的节点。在 “最低要求交互分数”中，设置最高置信度 （0.900），然后单击 “更新”。</li>
	<li>单击 “导出 ”以下载 .png 和 .tsv 格式的蛋白质-蛋白质相互作用 （PPI） 网络文本。</li>
</ol>4. 构建药物-成分-疾病-靶点网络
<ol><li>打开 Cytoscape 3.9.1 并导入步骤 3.4 中提到的 .tsv 文件。单击控制面板中的 样式 栏以优化网络节点的颜色、字体和侧面。</li>
	<li>对于网络拓扑分析，请使用 分析网络 功能。要获得枢纽基因，请在 Cytoscape 软件中使用 CytoHubba 。建立药物-成分-疾病-靶点网络。</li>
</ol>5. GO和KEGG富集分析
<ol><li>访问 Metascape 网站 （https://metascape.org/）。选择一个文件或将基因列表粘贴到对话框中，然后单击“提交”按钮。然后在“输入为物种”和“分析为物种”中选择智人;之后，启用自定义分析功能。</li>
	<li>在富集选项中，选择 GO Molecular Functions、GO Biological Processes、GO Cellular Components 和 KEGG Pathway 数据库。选中 Pick Selective GO Clusters，然后单击 Enrichment Analysis 按钮。完成进度条后，启动 “分析报告页面 ”以检索扩充结果。</li>
</ol>6. GEO基因芯片数据集分析
<ol><li>使用GEO2R工具（https://ncbi.nlm.nih.gov/geo/geo2r/）搜索和分析GEO基因芯片数据集（GDS3806），以研究不同数据组（对照组-非特应性皮炎;实验组-特应性皮炎）中中心基因的表达。</li>
	<li>进入GEO数据库网站（https://www.ncbi.nlm.nih.gov/geo/）。输入关键字或GEO加入，然后单击“搜索 ”按钮。选择最佳匹配结果。查找参考系列 （GSE26952）。</li>
	<li>进入GEO2R工具网站（https://ncbi.nlm.nih.gov/geo/geo2r/），在GEO加入 框中输入参考系列，点击 设置 按钮。选择 特应性皮炎 作为实验组，选择 非特应性对照 作为对照组，然后单击 “分析 ”按钮。计算完成后，将出现结果。</li>
</ol>7. 分子对接
<ol><li>打开TCMSP数据库，下载所选成分的3D结构。使用 化学名称 搜索框并搜索选定的成分名称以下载相应的 mol2 格式的 3D 结构文件。</li>
	<li>打开 RCSB 蛋白质数据库 （http://www.pdb.org/） 并下载关键靶标的晶体结构。在搜索框中，搜索目标名称，下载对应的pdb格式晶体结构文件。</li>
	<li>将成分和目标结构文件导入分析软件。通过单击 “编辑”>“删除水”来删除水分子。通过单击 “编辑”>“氢气”>“添加”来添加氢气。设置成分为配体，选择整个靶标作为受体，进行盲对接。</li>
	<li>确定分子对接的范围。<ol><li>依次选择受体和配体。单击 “网格”（Grid） >“网格框”（Grid Box ） 以调整网格框以包含整个模型。单击 “文件”>“关闭 保存电流”以保存网格框状态。以 gpf 格式保存文件。</li>
		<li>单击 “运行”>“运行 Autogrid4”>“参数文件名”>“浏览”，选择 gpf 文件，然后单击“ 启动 ”按钮。</li>
	</ol></li>
	<li>使用 AutoDock 4 执行分子对接。<ol><li>单击 Docking > Macromolecule > Set Rigid Filename 以选择受体。单击“ >配体对接”>打开/选择 选择配体。</li>
		<li>点击 “对接>搜索参数 ”设置操作算法，点击 “对接>对接参数 ”设置对接参数。选择 dpf 文件，然后单击“启动”按钮。以 dpf 格式保存文件。</li>
		<li>点击“ 分析>对接>打开”，选择DLG文件，点击“ 分析>大分子 ”打开受体，点击“分析 >构象>播放”， 点击“按能量排名 ”分析结果。单击 “设置播放”>“写入复合体 ”，将结果保存为 pdbqt 格式。</li>
	</ol></li>
	<li>将对接文件导入 PyMOL 软件以构建进一步的可视化。<ol><li>选择配体， 然后单击 “操作”>“查找 对象中其他原子>>极性接触 ”以显示配体与外部环境之间的氢键。单击 c 更改颜色。</li>
		<li>单击“ 操作”>“提取对象”。单击 “显示>棒 ”以显示受体的棒状结构。识别与配体相连的残基并显示棒状结构。</li>
		<li>单击 “隐藏>棒 ”以隐藏受体的棒状结构。单击“ 测量向导”> “，然后依次单击两个原子。单击 “残留物标签> ”以显示残留物的标签。如有必要，调整背景颜色和透明度。点击 文件 > 导出图像 as 保存图片。</li>
	</ol></li>
</ol>

肛门湿疹治疗中 SDG 的网络药理学和 GEO 数据集分析

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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Network+pharmacology:+curing+causal+mechanisms+instead+of+treating+symptoms.">Network pharmacology: curing causal mechanisms instead of treating symptoms.</a> Trends in Pharmacological Sciences. 43 (2), 136-150 (2022).</li><li>Wang, T., Zhou, Y., Wang, K., Jiang, X., Wang, J., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+and+validation+of+potential+molecular+targets+for+the+combination+of+Astragalus+membranaceus+and+Angelica+sinensis+in+the+treatment+of+atherosclerosis+based+on+network+pharmacology.">Prediction and validation of potential molecular targets for the combination of Astragalus membranaceus and Angelica sinensis in the treatment of atherosclerosis based on network pharmacology.</a> Medicine (Baltimore). 101 (26), e29762 (2022).</li><li>Jiang, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploration+of+Fuzheng+Yugan+mixture+on+COVID-19+based+on+network+pharmacology+and+molecular+docking.">Exploration of Fuzheng Yugan mixture on COVID-19 based on network pharmacology and molecular docking.</a> Medicine (Baltimore). 102 (3), e32693 (2023).</li><li>Dong, Y., Zhao, Q., Wang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Network+pharmacology-based+investigation+of+potential+targets+of+astragalus+membranaceous-angelica+sinensis+compound+acting+on+diabetic+nephropathy.">Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy.</a> Scientific Reports. 11 (1), 19496 (2021).</li><li>Wang, T., Jiang, X., Lu, Y., Ruan, Y., Wang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+and+integration+analysis+of+a+novel+prognostic+signature+associated+with+cuproptosis-related+ferroptosis+genes+and+relevant+lncRNA+regulatory+axis+in+lung+adenocarcinoma.">Identification and integration analysis of a novel prognostic signature associated with cuproptosis-related ferroptosis genes and relevant lncRNA regulatory axis in lung adenocarcinoma.</a> Aging (Albany NY). 15 (5), 1543-1563 (2023).</li><li>Wang, T., Jiang, X., Ruan, Y., Zhuang, J., Yin, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Based+on+network+pharmacology+and+in+vitro+experiments+to+prove+the+effective+inhibition+of+myocardial+fibrosis+by+Buyang+Huanwu+decoction).">Based on network pharmacology and in vitro experiments to prove the effective inhibition of myocardial fibrosis by Buyang Huanwu decoction).</a> Bioengineered. 13 (5), 13767-13783 (2022).</li></ol>

作者没有什么可透露的。

特应性皮炎是一种特殊形式的湿疹，与湿疹具有共同的潜在机制。被认为与这种情况相关的中心基因是 TNF、MAPK14 和 CASP3。SDG对肛门湿疹的治疗作用主要归因于其通过这三个枢纽基因对TNF和MAPK信号通路的作用17。
SDG包括五种不同的药物：天然靛蓝、金柏、煅烧石膏、炉甘石和中国瘿。在中药中，煅烧石膏和炉甘石可以起到促进伤口愈合和干燥湿气的作用，而...

肛门湿疹是一种影响肛周区域和粘膜的过敏性皮肤病，表现出多种临床表现1.特征性症状包括肛门红斑、丘疹、水疱、糜烂、渗出物和结痂。这些症状主要是由于受影响区域的划痕、增厚和粗糙而引起的 2.
肛门湿疹的特征是病程长、反复发作和具有挑战性的治疗，会对患者的身心健康产生不良影响3.肛门湿疹的发病机制尚不清楚，现代医学提示可能与局部肛门病变、饮食、环境、遗传等因素有关4。肛门湿疹的治疗除了避免接触刺激物和潜在过敏原外，主要集中在抑制炎症、抗过敏、缓解瘙痒等方法上5。
SDG已被广泛用于治疗肛门湿疹和其他肛门疾病。SDG调节肛门皮肤渗出，减少水分，修复肛门皮肤，并有效解决瘙痒6,7,8。此外，SDG具有调节肛门菌群的潜力，从而改善肛门湿疹9,10。
网络药理学是人工智能和大数据领域中一种新颖的、跨学科的前沿生物信息学方法，为中医药提供了深入的探索。该学科强调从生态网络视角系统阐述药物与疾病之间的分子关联规则。它已被广泛用于各个方面，包括识别草药提取物中的关键活性成分、破译其整体作用机制、制定药物组合以及研究处方相容性。传统中药处方具有多组分、多靶点的特点，对网络药理学领域具有实质性的适应性。在这种方法的推动下，复杂中医药体系的检验出现了新的视角，为临床应用合理化和药物创新提供了强有力的技术支持11,12,13,14。
本研究旨在探讨SDG治疗肛门湿疹的有效性机制。这项调查工作旨在通过网络药理学和 GEO 数据集的协同整合来阐明局部给药的机制。这些发现为SDG在肛门湿疹管理中的疗效和潜在机制提供了宝贵的见解，表明其作为该病症的有效治疗方法的潜力。该研究的详细工作流程图如 图 1 所示。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>AutoDockTools</td>
			<td>AutoDock</td>
			<td>https://autodocksuite.scripps.edu/adt/</td>
			<td></td>
		</tr>
		<tr>
			<td>Cytoscape 3.9.1&#160;</td>
			<td>Cytoscape</td>
			<td>https://cytoscape.org/</td>
			<td></td>
		</tr>
		<tr>
			<td>GeneCards database&#160;</td>
			<td>GeneCards</td>
			<td>https://www.genecards.org</td>
			<td></td>
		</tr>
		<tr>
			<td>GEO database</td>
			<td>National Center for Biotechnology Information</td>
			<td>https://www.ncbi.nlm.nih.gov/geo/</td>
			<td></td>
		</tr>
		<tr>
			<td>GEO2R tool&#160;</td>
			<td>National Center for Biotechnology Information</td>
			<td>https://ncbi.nlm.nih.gov/geo/geo2r/</td>
			<td></td>
		</tr>
		<tr>
			<td>Metascape</td>
			<td>Metascape</td>
			<td>https://metascape.org/</td>
			<td></td>
		</tr>
		<tr>
			<td>Online Mendelian inheritance in man database</td>
			<td>OMIM</td>
			<td>https://www.omim.org</td>
			<td></td>
		</tr>
		<tr>
			<td>RCSB protein database&#160;</td>
			<td>RCSB Protein Data Bank (RCSB PDB)</td>
			<td>http://www.pdb.org/</td>
			<td></td>
		</tr>
		<tr>
			<td>STRING database&#160;</td>
			<td>STRING</td>
			<td>https://string-db.org/</td>
			<td></td>
		</tr>
		<tr>
			<td>Swiss ADME database&#160;</td>
			<td>Swiss Institute of Bioinformatics</td>
			<td>http://www.swissadme.ch/index.php</td>
			<td></td>
		</tr>
		<tr>
			<td>Traditional Chinese Medicine system&#39;s pharmacology database (TCMSP)</td>
			<td>Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform</td>
			<td>http://tcmspw.com/tcmsp.php</td>
			<td></td>
		</tr>
		<tr>
			<td>Venny2.1</td>
			<td>BioinfoGP</td>
			<td>https://bioinfogp.cnb.csic.es/tools/venny/index.html</td>
			<td></td>
		</tr>
	</tbody>
</table>

the efficacy and underlying pathway mechanisms of shidugao treatment for anus eczema based on geo datasets and network pharmacology

肛门湿疹是一种影响肛门周围区域的慢性复发性炎症性皮肤病。虽然病变主要发生在肛门和肛周皮肤，但它们也可以延伸到会阴或生殖器。石度高 （SDG） 已被发现具有显着的修复特性，可防止肛门瘙痒、控制渗出、减少水分和修复皮肤。然而，SDG对肛门湿疹的遗传靶点和药理机制尚未得到全面阐明和讨论。因此，本研究采用网络药理学方法，并利用基因表达综合（GEO）数据集来研究基因靶点。此外，还建立了蛋白质-蛋白质相互作用网络（PPI），从而在“药物-靶点-疾病”相互作用网络中鉴定了149个靶点，其中59个被认为是枢纽基因。
通过利用京都基因和基因组百科全书（KEGG）和基因本体（GO）分析评估SDG在治疗肛周湿疹中的基因功能。随后，采用分子对接方法验证了网络药理学分析中确定的SDG的抗肛周湿疹功能和潜在通路。在肛门湿疹治疗中，与SDG靶向基因和蛋白质相关的生物过程主要包括细胞因子介导的反应、炎症反应和对脂多糖的反应等。通路富集和功能注释分析的结果表明，SDG通过调节志贺菌病和单纯疱疹病毒1型感染途径，在预防和管理肛门湿疹方面发挥着至关重要的作用。网络药理学和GEO数据库分析证实了SDG在治疗肛门湿疹方面的多靶点性质，特别是通过调节TNF、MAPK14和CASP3，它们是TNF和MAPK信号通路中的关键枢纽靶点。这些发现为进一步研究SDG对肛门湿疹的治疗机制提供了明确的方向，同时强调了其作为这种衰弱性疾病的有效治疗方法的潜力。

肛门湿疹相关基因、SDG靶基因和常见靶点 在基因卡中筛选了958个潜在的候选基因，在OMIM数据库中筛选了634个，同时排除了重复基因。为了全面了解肛门湿疹相关基因，将多个数据库的发现合并在一起，总共产生了958个不同的基因。因此，精心制定了针对肛门湿疹的蛋白质-蛋白质相互作用网络（PPI）。SDG由五种传统中药组成，即靛蓝、金柏、煅烧石膏、炉甘石和中胆15...

Watch this Scientific Journal Video about The Efficacy and Underlying Pathway Mechanisms of ShiDuGao Treatment for Anus Eczema Based on GEO Datasets and Network Pharmacology at JoVE.com

作者聚焦：探索 ShiDuGao 在肛门湿疹治疗中的多靶点方法

这项调查工作旨在通过网络药理学和基因表达综合 （GEO） 数据集的协同整合来阐明局部给药的机制。本文评价了石度高（SDG）治疗肛门湿疹的可行性、靶点和机制。

基于GEO数据集和网络药理学的石都高治疗肛门湿疹的疗效及潜在通路机制

Anus eczema is a chronic and recurrent inflammatory skin disease affecting the area around the anus. While the lesions primarily occur in the anal and ...

the-efficacy-underlying-pathway-mechanisms-shidugao-treatment-for

Research

JoVE Journal

Medicine

The Efficacy and Underlying Pathway Mechanisms of ShiDuGao Treatment for Anus Eczema Based on GEO Datasets and Network Pharmacology

689 次观看.  Tianjin Medical University General Hospital. 1 本文评价了十度高治疗肛门湿疹的可行性、靶点 2 和机制。3 网络药理学和 GEO 数据库分析 4 证实了 SDG 5 治疗肛门湿疹的多靶点性质，6 特别是通过调节 TNF 和 APK 14、7 和 CASP3、8 它们是 TNF 9 和 MAPK 信号通路中的关键枢纽靶点。10 这些资金为进一步研究可持续发展目标提供了明确的方向 1112 肛门湿疹的治疗机制，13 同时强调其潜力 14 作为这种使人?...

视频: 作者聚焦：探索 ShiDuGao 在肛门湿疹治疗中的多靶点方法

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

MRI引导dmPFC-rTMS治疗作为治疗难治性抑郁症

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

科研

医学

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

在耐药性颞叶癫痫患者卵圆孔电极记录的网络分析

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine

The gut is the largest endocrine organ of the body, producing more than 15 different peptide hormones that regulate appetite and food intake, digestion, nutrient absorption and distribution, and post-prandial glucose excursions. Understanding the molecular mechanisms that regulate gut hormone secretion is fundamental for understanding and translating gut hormone physiology. Traditionally, the mechanisms underlying gut hormone secretion are either studied in vivo (in experimental animals or humans) or using gut hormone-secreting primary mucosal cell cultures or cell lines. Here, we introduce an isolated perfused rat small intestine as an alternative method for studying gut hormone secretion. The virtues of this model are that it relies on the intact gut, meaning that it recapitulates most of the physiologically important parameters responsible for the secretion in in vivo studies, including mucosal polarization, paracrine relationships and routes of perfusion/stimulus exposure. In addition, and unlike in vivo studies, the isolated perfused rat small intestine allows for almost complete experimental control and direct assessment of secretion. In contrast to in vitro studies, it is possible to study both the magnitude and the dynamics of secretion and to address important questions, such as what stimuli cause secretion of different gut hormones, from which side of the gut (luminal or vascular) is secretion stimulated, and to analyze in detail molecular sensors underlying the secretory response. In addition, the preparation is a powerful model for the study of intestinal absorption and details regarding the dynamics of intestinal absorption including the responsible transporters.

Here, we present a powerful and physiological model to study the molecular mechanisms underlying gut hormone secretion and intestinal absorption &#8212; the isolated perfused rat small intestine.

利用隔离的完美大鼠小肠进行肠道激素分泌的机制

The gut is the largest endocrine organ of the body, producing more than 15 different peptide hormones that regulate appetite and food intake, digestion, ...

Diagnosis and Surgical Treatment of Human Brucellar Spondylodiscitis

Brucellar spondylodiscitis (BS) is the most prevalent and significant osteoarticular presentation of human Brucellosis, which is commonly manifested in pastoral communities. It is difficult to differentially diagnose and usually leads to irreversible neurologic deficits and spinal deformities. The initial diagnosis of BS is based on clinical findings and radiographic assessments, and the confirmed diagnosis should be established by the isolation of Brucella species from the blood and/or the standard tube agglutination test. Differential diagnosis of multifocal BS from either degenerative disc diseases or tuberculosis is especially highlighted. The surgical approach, either endoscopic or open, is demonstrated in detail, accompanied by radiographic evidence of structural compression or severe instability. Further, the crucial surgical steps, including single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation, are explained. Moreover, perioperative care and postoperative rehabilitation are also addressed. Taken together, this clinical algorithm presents a practical guide that has yielded substantially satisfactory outcomes in the past decades, which can also be introduced for large-scale application to manage human BS, especially in endemic regions.

We describe a clinical algorithm, based on decades of front-line experience of diagnosis and surgical treatment of human Brucellar spondylodiscitis in the largest medical center of the China's Xinjiang Pastoral Area.

人类布鲁塞拉性皮诺皮诺皮炎的诊断和手术治疗

Brucellar spondylodiscitis (BS) is the most prevalent and significant osteoarticular presentation of human Brucellosis, which is commonly manifested in ...

Laser-Induced Action Potential-Like Measurements of Cardiomyocytes on Microelectrode Arrays for Increased Predictivity of Safety Pharmacology

Life-threatening drug-induced cardiac arrhythmia is often preceded by prolonged cardiac action potentials (AP), commonly accompanied by small proarrhythmic membrane potential fluctuations. The shape and time course of the repolarizing fraction of the AP can be pivotal for the presence or absence of arrhythmia.
Microelectrode arrays (MEA) allow easy access to cardiotoxic compound effects via extracellular field potentials (FP). Although a powerful and well-established tool in research and cardiac safety pharmacology, the FP waveform does not allow to infer the original AP shape due to the extracellular recording principle and the resulting intrinsic alternating current (AC) filtering.
A novel device, described here, can repetitively open the membrane of cardiomyocytes cultivated on top of the MEA electrodes at multiple cultivation time points, using a highly focused nanosecond laser beam. The laser poration results in transforming the electrophysiological signal from FP to intracellular-like APs (laser-induced AP, liAP) and enables the recording of transcellular voltage deflections. This intracellular access allows a better description of the AP shape and a better and more sensitive classification of proarrhythmic potentials than regular MEA recordings. This system is a revolutionary extension to the existing electrophysiological methods, permitting accurate evaluation of cardiotoxic effect with all advantages of MEA-based recordings (easy, acute, and chronic experiments, signal propagation analysis, etc.).

The combination of laser poration and microelectrode arrays (MEA) allows action potential-like recordings of cultivated primary and stem cell-derived cardiomyocytes. The waveform shape provides superior insight into test compounds' mode of action than standard recordings. It links patch-clamp and MEA readout to further optimize cardio safety research in the future.

激光诱导动作电位样测量微电极阵列上的心肌细胞，以提高安全药理学的预测性

Life-threatening drug-induced cardiac arrhythmia is often preceded by prolonged cardiac action potentials (AP), commonly accompanied by small ...

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic effects of Zadi-5 against depression have been indicated in previously reported clinical studies, the identity and impact of the active pharmaceutical compounds present in the drug have not been fully elucidated.&#160;This study used network pharmacology to predict the drug composition and identify the therapeutically active compounds in Zadi-5 pills. Here, we established a rat model of chronic unpredicted mild stress (CUMS) and conducted an open field test (OFT), Morris water maze (MWM) analysis, and sucrose consumption test (SCT) to investigate the potential therapeutic efficacy of Zadi-5 in depression. This study aimed to demonstrate Zadi-5&#39;s therapeutic effects for depression and predict the critical pathway of the action of Zadi-5 against the disorder. The vertical and horizontal scores (OFT), SCT, and zone crossing numbers of the fluoxetine (positive control) and Zadi-5 groups were significantly higher (P &#60; 0.05) than those of the CUMS group rats without treatment. According to the results of network pharmacology analysis, the PI3K-AKT pathway was found to be essential for the antidepressant effect of Zadi-5.

The present protocol describes a method for the behavioral test validation and bioinformatical prediction of the therapeutic efficacy of Zadi-5, a traditional Mongolian medicine, in depression.

基于行为和网络药理学的蒙古医学Zadi-5在抑郁症大鼠模型中的分析

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic ...

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

This study reveals the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma based on network pharmacology and experimental verification. The study also demonstrates that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

毛滴虫对肺腺癌作用机制的网络药理学预测及实验验证

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and ...

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug against hyperlipidemia in Traditional Chinese Medicine (TCM) and Indian Medicine theories, however the potential mechanism requires further exploration. The present research aims to reveal the mechanism of FP against hyperlipidemia based on an integrated strategy combining network pharmacology prediction with metabolomics validation. A high-fat diet (HFD)-induced mice model was established by evaluating the plasma lipid levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Network pharmacology was applied to find out the active ingredients of FP and potential targets against hyperlipidemia. Metabolomics of plasma and liver were performed to identify differential metabolites and their corresponding pathways among the normal group, model group, and intervention group. The relationship between network pharmacology and metabolomics was further constructed to obtain a comprehensive view of the process of FP against hyperlipidemia. The obtained key target proteins were verified by molecular docking. These results reflected that FP improved the plasma lipid levels and liver injury of hyperlipidemia induced by a HFD. Gallic acid, quercetin, and beta-sitosterol in FP were demonstrated as the key active compounds. A total of 16 and six potential differential metabolites in plasma and liver, respectively, were found to be involved in the therapeutic effects of FP against hyperlipidemia by metabolomics. Further, integration analysis indicated that the intervention effects were associated with CYP1A1, AChE, and MGAM, as well as the adjustment of L-kynurenine, corticosterone, acetylcholine, and raffinose, mainly involving tryptophan metabolism pathway. Molecular docking ensured that the above ingredients acting on hyperlipidemia-related protein targets played a key role in lowering lipids. In summary, this research provided a new possibility for preventing and treating hyperlipidemia.

The present protocol describes an integrated strategy for exploring the key targets and mechanisms of Fructus Phyllanthi against hyperlipidemia based on network pharmacology prediction and metabolomics verification.

网络药理学预测及代谢组学验证 凤仙花抗高脂血症的机制

Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug ...

病毒性脑炎治疗的系统评价和荟萃分析

The Adjuvant Efficacy of Angong Niuhuang Pill in the Treatment of Viral Encephalitis: A Meta-Analysis of Randomized Controlled Trials

This meta-analysis aims to evaluate the efficacy of Angong Niuhuang Pill (ANP) as an adjuvant therapy in the treatment of viral encephalitis. Seven databases (PubMed, Cochrane Library, Embase, SinoMed, CNKI, VIP and WanFang) were included for literature retrieval from inception to July 2023. Randomized controlled trials comparing ANP plus conventional therapy with conventional therapy alone were eligible. Pooled effect sizes and 95% confidence intervals (CIs) were calculated for evaluating efficacy and safety. Sensitivity analysis and publication bias assessments were performed for analyzing the inconclusiveness of findings. 13 studies involving 1045 cases were included for meta-analysis. Adjuvant treatment with ANP increased the probability of the total effective rate by 17% compared with conventional treatment (Risk ratios (RR) = 1.17, 95%CI [1.08, 1.27]). The disappearance time of clinical syndromes and signs was significantly decreased after adjuvant treatment with ANP, including the time of defervescence (weighted mean difference (WMD) = -1.59, 95%CI [-2.09, -1.09]), the time of consciousness recovery (WMD = -1.79, 95%CI [-2.06, -1.51]), the time of headache disappearance (WMD = -1.51, 95%CI [-1.93, -1.08]), the time of tic disappearance (WMD = -1.88, 95%CI [-2.39, -1.36]). The adjuvant efficacy of ANP for treating viral encephalitis (VE) appears to improve the total effective rate and shorten the disappearance time of clinical syndromes. More high-quality randomized controlled trials (RCTs) are needed to support our findings.

作者聚焦：评价安宫牛黄丸治疗病毒性脑炎的辅助疗效和安全性

Here, we present a protocol to analyze the effectiveness and safety of Angong Niuhuang Pill in the treatment of viral encephalitis.

安公牛黄丸治疗病毒性脑炎的辅助疗效：随机对照试验的Meta分析

This meta-analysis aims to evaluate the efficacy of Angong Niuhuang Pill (ANP) as an adjuvant therapy in the treatment of viral encephalitis. Seven ...