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Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer’s disease model 补肾天遂汤通过PI3K信号通路调节阿尔茨海默病模型的突触损伤
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.008
Shan Hui , Qing Zheng , Hongli Li , Lemei Zhu , Beibei Wu , Lihui Liang , Jingjing Yang
<div><h3>Objective</h3><div>To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction (补肾填髓方, BSTSD) and its active component icariin on Alzheimer’s disease (AD).</div></div><div><h3>Methods</h3><div>(i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, <em>n</em> = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, <em>n</em> = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, <em>n</em> = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), A<em>β</em><sub>25-35</sub> group (treated with 20 μmol/L A<em>β</em><sub>25-35</sub> for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L A<em>β</em><sub>25-35</sub> for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L A<em>β</em><sub>25-35</sub> for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR].</div></div><div><h3>Results</h3><div>(i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (<em>P</em> < 0.01) and the frequency of crossing the original platform was significantly increased (<em>P</em> < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (<em>P</em> < 0.01), and the width of synaptic gap was decreased (<em>P</em> < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (<em>P</em> > 0.05), and alleviated the cell viability decline induced by A<em>β</em><sub>25-35</sub> (<em>P</em> < 0.01). Western blot results showed that compared with A<em>β</em><sub>25-35</sub> group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly in
目的探讨补肾天遂汤及其有效成分淫羊藿苷对阿尔茨海默病(AD)的治疗作用及机制。方法(1)动物实验。本研究采用SPF级雄性C57BL/6J野生型(WT)小鼠和APP/PS1双转基因小鼠进行实验。将动物分为三组:WT组(WT小鼠,n = 5,每天接受蒸馏水)、APP/PS1组(APP/PS1双转基因小鼠,n = 5,每天接受蒸馏水)和BSTSD组[APP/PS1双转基因小鼠,n = 5,以27 g/(kg·d)的剂量给予BSTSD混悬液,持续90 d]。采用Morris水迷宫(MWM)评估认知功能。实验结束后,采集海马组织,通过苏木精-伊红(HE)染色和透射电镜(TEM)分析锥体细胞和突触形态。(ii)细胞实验。HT-22细胞分为对照组(治疗),一个β25 - 35组(治疗20μmol / L的β25 - 24 h), icariin集团(预处理与20μ,淫羊藿60分钟浓度mol / L,紧随其后的是20μmol / Lβ25 - 35一个额外的24 h),淫羊藿+ LY294002浓度和组(治疗20μ,淫羊藿和20μ摩尔浓度mol / L / L LY294002(抑制剂phosphoinostitide 3-kinases PI3K信号通路)60分钟,然后暴露于20μmol / L的β25 - 24小时),和细胞生存能力测量。Western blot检测突触相关蛋白[synaptophysin (SYP)和突触后密度-95 (PSD-95)]和PI3K信号通路相关蛋白[磷酸化(p)-PI3K/PI3K, p蛋白激酶B (Akt)/Akt和雷帕霉素p-mechanistic target of rapamycin (mTOR)/mTOR]的表达水平。与APP/PS1组比较,BSTSD组小鼠逃避潜伏期显著缩短(P <;0.01),穿越原平台的频率显著增加(P <;0.01)。形态学观察显示,BSTSD处理后海马CA1区锥体细胞排列更加规则,细胞核染色均匀,空泡样改变减少。透射电镜显示,与APP/PS1组相比,BSTSD治疗组突触活性区长度增加(P <;0.01),突触间隙宽度减小(P <;0.01)。(ii)细胞实验。当淫羊藿苷浓度不大于20 μmol/L时,对HT-22细胞无明显毒性作用(P >;0.05),并减轻了Aβ25-35诱导的细胞活力下降(P <;0.01)。Western blot结果显示,与Aβ25-35组相比,淫羊藿苷组P -PI3K/PI3K、P -Akt/Akt、P -mTOR/mTOR比值显著升高(P <;0.01),而SYP和PSD-95蛋白表达水平升高(P <;0.01)。LY294002 (P <;0.01)。结论bstsd和淫羊藿苷可增强AD模型的认知功能和突触完整性,并通过激活PI3K/Akt/mTOR通路提供潜在的治疗策略。
{"title":"Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer’s disease model","authors":"Shan Hui ,&nbsp;Qing Zheng ,&nbsp;Hongli Li ,&nbsp;Lemei Zhu ,&nbsp;Beibei Wu ,&nbsp;Lihui Liang ,&nbsp;Jingjing Yang","doi":"10.1016/j.dcmed.2024.12.008","DOIUrl":"10.1016/j.dcmed.2024.12.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction (补肾填髓方, BSTSD) and its active component icariin on Alzheimer’s disease (AD).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;(i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, &lt;em&gt;n&lt;/em&gt; = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, &lt;em&gt;n&lt;/em&gt; = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, &lt;em&gt;n&lt;/em&gt; = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; group (treated with 20 μmol/L A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR].&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;(i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (&lt;em&gt;P&lt;/em&gt; &lt; 0.01) and the frequency of crossing the original platform was significantly increased (&lt;em&gt;P&lt;/em&gt; &lt; 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (&lt;em&gt;P&lt;/em&gt; &lt; 0.01), and the width of synaptic gap was decreased (&lt;em&gt;P&lt;/em&gt; &lt; 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (&lt;em&gt;P&lt;/em&gt; &gt; 0.05), and alleviated the cell viability decline induced by A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; (&lt;em&gt;P&lt;/em&gt; &lt; 0.01). Western blot results showed that compared with A&lt;em&gt;β&lt;/em&gt;&lt;sub&gt;25-35&lt;/sub&gt; group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly in","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 284-293"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143262515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic characteristics of Qi-Yin deficiency and heat stagnation in liver meridian patterns of dry eye based on tear metabolomics 基于泪液代谢组学的干眼症肝经络气阴虚热郁的代谢特征
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.007
Xie Mingxia , Cai Zengyun , Li Junyao , Tan Jiaren , Liu Pei , Yu Yanlan , Jiao Luojia
<div><h3>Objective</h3><div>To explore the metabolic differences between dry eye patients with Qi-Yin deficiency and heat stagnation in liver meridian patterns, and clarify their metabolic characteristics.</div></div><div><h3>Methods</h3><div>Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1, 2020, to October 30, 2021 were enrolled as the research participants in the study. They were assigned to two groups based on traditional Chinese medicine (TCM) syndrome types: heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group. Healthy volunteers who underwent health check-ups in the Health Management Department were included as healthy group following the random number table method. The tears of the patients and the healthy volunteer participants were tested by high-performance liquid chromatography-mass spectrometry (LC-MS). The differential metabolites were screened out by multivariate statistical analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed on the differential metabolites. Finally, the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites.</div></div><div><h3>Results</h3><div>A total of 32 dry eye patients were enrolled, including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern. Fourteen healthy volunteers were included as healthy group. There were no significant differences in baseline characteristics among the three groups (<em>P</em> > 0.05). A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group, mainly including lipids, lipid-like molecules, organic acids and their derivatives, organic heterocyclic compounds, and nucleosides and their analogues. For heat stagnation in liver meridian pattern group, 112 metabolites were determined, mainly including organic acids and their derivatives, lipids, and lipid-like molecules. The KEGG enrichment results of pathways and the relative content analysis of differential markers demonstrate that purine metabolism and caffeine metabolism pathways are common metabolic characteristics of all dry eyes. Among them, deoxyinosine monophosphate (dIMP) and 2-(formamido)-N1-(5-phospha-D-ribosyl) acetamidine can serve as their biomarkers. The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation, ovarian steroidogenesis, cholesterol metabolism, pyrimidine metabolism, and bile secretion (<em>P</em> < 0.05). Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine, leucine, and isoleucine biosynthesis pathways (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Metabolomics can be used as an effective basis for TCM syndrome classif
目的探讨气阴虚热滞型干眼症肝经证的代谢差异,阐明其代谢特点。方法选取2020年10月1日至2021年10月30日在湖南中医药大学第一医院眼科病房和门诊部就诊的干眼症患者作为研究对象。根据中医证型分为肝经热郁证组和气阴虚证组。采用随机数字表法将在健康管理部门进行健康检查的健康志愿者作为健康组。采用高效液相色谱-质谱联用技术(LC-MS)检测患者和健康志愿者的眼泪。通过多元统计分析筛选出差异代谢物,并对差异代谢物进行京都基因与基因组百科全书(KEGG)途径富集。最后进行差异蛋白与代谢物的关联分析,对代谢物进行验证和补充。结果共纳入32例干眼症患者,其中肝经热滞型16例,气阴虚型16例。选取14名健康志愿者作为健康组。三组患者的基线特征无显著差异(P >;0.05)。气阴虚证组共检测到412种生物标志物,主要包括脂类、类脂类分子、有机酸及其衍生物、有机杂环化合物、核苷及其类似物等。肝经证热郁组测定代谢产物112种,主要包括有机酸及其衍生物、脂类及类脂类分子。通路的KEGG富集结果和差异标记物的相对含量分析表明,嘌呤代谢和咖啡因代谢通路是所有干眼症的共同代谢特征。其中,单磷酸脱氧肌苷(dIMP)和2-(甲胺)- n1 -(5-磷酸- d -核糖基)acetamidine可作为它们的生物标志物。气阴虚证型的主要特点是赖氨酸降解、卵巢类固醇生成、胆固醇代谢、嘧啶代谢、胆汁分泌等代谢途径明显增强(P <;0.05)。肝经络热滞干眼主要表现为缬氨酸、亮氨酸和异亮氨酸生物合成途径的抑制(P <;0.05)。结论代谢组学可作为中医证候分型的有效依据。干眼症不同证型在代谢物类型和浓度上表现出典型特征,与中医辨证分型相对应。本研究初步证实了中医辨证分型的合理性,为干眼症的发病机制及药物研发提供了重要参考。
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引用次数: 0
Construction and optimization of traditional Chinese medicine constitution prediction models based on deep learning 基于深度学习的中药体质预测模型构建与优化
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.004
Zhang Xinge, Xu Qiang, Wen Chuanbiao, Luo Yue
<div><h3>Objective</h3><div>To cater to the demands for personalized health services from a deep learning perspective by investigating the characteristics of traditional Chinese medicine (TCM) constitution data and constructing models to explore new prediction methods.</div></div><div><h3>Methods</h3><div>Data from students at Chengdu University of Traditional Chinese Medicine were collected and organized according to the 24 solar terms from January 21, 2020, to April 6, 2022. The data were used to identify nine TCM constitutions, including balanced constitution, Qi deficiency constitution, Yang deficiency constitution, Yin deficiency constitution, phlegm dampness constitution, damp heat constitution, stagnant blood constitution, Qi stagnation constitution, and specific-inherited predisposition constitution. Deep learning algorithms were employed to construct multi-layer perceptron (MLP), long short-term memory (LSTM), and deep belief network (DBN) models for the prediction of TCM constitutions based on the nine constitution types. To optimize these TCM constitution prediction models, this study introduced the attention mechanism (AM), grey wolf optimizer (GWO), and particle swarm optimization (PSO). The models’ performance was evaluated before and after optimization using the F1-score, accuracy, precision, and recall.</div></div><div><h3>Results</h3><div>The research analyzed a total of 31 655 pieces of data. (i) Before optimization, the MLP model achieved more than 90% prediction accuracy for all constitution types except the balanced and Qi deficiency constitutions. The LSTM model's prediction accuracies exceeded 60%, indicating that their potential in TCM constitutional prediction may not have been fully realized due to the absence of pronounced temporal features in the data. Regarding the DBN model, the binary classification analysis showed that, apart from slightly underperforming in predicting the Qi deficiency constitution and damp heat constitution, with accuracies of 65% and 60%, respectively. The DBN model demonstrated considerable discriminative power for other constitution types, achieving prediction accuracy rates and area under the receiver operating characteristic (ROC) curve (AUC) values exceeding 70% and 0.78, respectively. This indicates that while the model possesses a certain level of constitutional differentiation ability, it encounters limitations in processing specific constitutional features, leaving room for further improvement in its performance. For multi-class classification problem, the DBN model’s prediction accuracy rate fell short of 50%. (ii) After optimization, the LSTM model, enhanced with the AM, typically achieved a prediction accuracy rate above 75%, with lower performance for the Qi deficiency constitution, stagnant blood constitution, and Qi stagnation constitution. The GWO-optimized DBN model for multi-class classification showed an increased prediction accuracy rate of 56%, while the PSO-optimized model
目的通过调查中医体质数据的特点,构建模型,探索新的预测方法,从深度学习的角度满足个性化健康服务的需求。方法收集成都中医药大学学生在2020年1月21日至2022年4月6日期间,按24节气进行数据整理。利用数据对9种中医体质进行鉴定,包括平衡体质、气虚体质、阳虚体质、阴虚体质、痰湿体质、湿热体质、瘀血体质、气滞体质和特定遗传易感体质。采用深度学习算法构建多层感知器(MLP)、长短期记忆(LSTM)和深度信念网络(DBN)模型,基于9种体质类型对中医体质进行预测。为了优化中药体质预测模型,本研究引入了注意机制(AM)、灰狼优化器(GWO)和粒子群优化(PSO)。采用f1评分、准确率、精密度和召回率对模型优化前后的性能进行评价。结果本研究共分析了31 655份数据。(i)优化前,除平衡体质和气虚体质外,MLP模型对所有体质类型的预测准确率均在90%以上。LSTM模型的预测精度超过60%,表明由于数据中缺乏明显的时间特征,LSTM模型在中医体质预测中的潜力可能没有得到充分发挥。DBN模型在预测气虚体质和湿热体质方面的准确率分别为65%和60%,二元分类分析结果显示,DBN模型在预测气虚体质和湿热体质方面表现略差。DBN模型对其他体质类型具有较强的判别能力,预测准确率超过70%,受试者工作特征曲线下面积(AUC)超过0.78。这说明该模型虽然具有一定的体质区分能力,但在处理特定体质特征方面存在一定的局限性,其性能还有进一步提升的空间。对于多类分类问题,DBN模型的预测准确率不足50%。(ii)优化后,经AM增强的LSTM模型的预测准确率一般在75%以上,但对气虚体质、瘀血体质、气滞体质的预测准确率较低。gwo优化后的DBN模型对多类分类的预测准确率提高到56%,而pso优化后的模型预测准确率下降到37%。两种算法优化后的GWO-PSO-DBN模型预测准确率提高了54%。结论本研究构建了中医体质预测的MLP、LSTM和DBN模型,并基于不同的优化算法对模型进行了改进。结果表明,MLP模型具有较好的预测效果,LSTM和DBN模型具有较好的预测效果,但存在一定的局限性。本研究也为中医体质预测模型的建立和优化策略提供了新的技术参考,为非疾病治疗提供了新的思路。
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引用次数: 0
Analysis on pulse features of coronary heart disease patients with or without a history of ischemic stroke 有或无缺血性脑卒中史冠心病患者脉搏特征分析
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.006
Li Xin , Li Wei , Ng Man-In, Parry Natalie Ann, Li Siqi, Li Rui, Guo Rui

Objective

To evaluate the capability of wrist pulse analysis in distinguishing three physiological and pathological conditions: healthy individuals, coronary heart disease (CHD) patients without a history of ischemic stroke, and CHD patients with a history of ischemic stroke.

Methods

Study participants were recruited from Shuguang East Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, and Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, from April 15 to September 15, 2021. They were categorized into three groups: healthy controls (Group 1), CHD patients without a history of ischemic stroke (Group 2), and CHD patients with a history of ischemic stroke (Group 3). The wrist pulse signals of the study participants were non-invasively collected using a pulse diagnosis instrument. The linear time-domain features and nonlinear time-series multiscale entropy (MSE) features of the pulse signals were extracted using time-domain analysis and the MSE methods, which were subsequently compared between groups. Based on these extracted features, a recognition model was developed using a random forest (RF) algorithm. The classification performance of the models was evaluated using metrics, including accuracy, precision, recall, and F1-score derived from confusion matrix as well as the area under the receiver operating characteristics (ROC) curve (AUC).

Results

A total of 189 participants were enrolled, with 63 in Group 1, 61 in Group 2, and 65 in Group 3. Compared with Group 1, Group 2 showed significant increases in pulse features H2/H1, H3/H1, W1, W2, and W2/T, and decreased in MSE1 – MSE7 (P < 0.05), while Group 3 showed significant increases in pulse features T5/T4, T, H1/T1, W1, W2, AS, and Ad, and decreased in MSE1 – MSE20 (P < 0.05). Compared with Group 2, Group 3 demonstrated notable increases in H1/T1 and As (P < 0.05). The RF model achieved precision of 80.00%, 61.54%, and 61.54%, recall of 74.29%, 60.00%, and 68.97%, F1-scores of 70.04%, 60.76%, and 65.04%, and AUC values of 0.92, 0.74, and 0.81 for Groups 1, 2, and 3, respectively. The overall accuracy was 67.69%, with micro-average AUC of 0.83 and macro-average AUC of 0.82.

Conclusion

Differences in pulse features reflect variations in arterial compliance, peripheral resistance, cardiac afterload, and pulse signal complexity among healthy individuals, CHD patients without a history of ischemic stroke, and those with such a history. The developed pulse-based recognition model holds the potential in distinguishing between these three groups, offering a novel diagnostic reference for clinical practice.
目的评价腕部脉搏分析对健康人、无缺血性脑卒中史的冠心病患者和有缺血性脑卒中史的冠心病患者三种生理病理状况的鉴别能力。研究对象于2021年4月15日至9月15日从上海中医药大学附属曙光东方医院、岳阳中西医结合医院和上海市中医医院招募。他们被分为三组:健康对照组(1组)、无缺血性卒中史的冠心病患者(2组)和有缺血性卒中史的冠心病患者(3组)。研究参与者的手腕脉搏信号使用脉搏诊断仪无创采集。采用时域分析和MSE方法提取脉冲信号的线性时域特征和非线性时间序列多尺度熵(MSE)特征,并进行组间比较。在此基础上,利用随机森林(RF)算法建立识别模型。使用指标评估模型的分类性能,包括准确度、精密度、召回率和由混淆矩阵得出的f1分数以及受试者工作特征(ROC)曲线下的面积。结果共入组189例,其中组1 63例,组2 61例,组3 65例。与1组比较,2组脉搏特征H2/H1、H3/H1、W1、W2、W2/T显著升高,MSE1 - MSE7显著降低(P <;0.05),而组3脉搏特征T5/T4、T、H1/T1、W1、W2、AS、Ad显著升高,MSE1 - MSE20显著降低(P <;0.05)。与2组比较,3组H1/T1和As明显升高(P <;0.05)。RF模型的准确率分别为80.00%、61.54%和61.54%,召回率分别为74.29%、60.00%和68.97%,f1得分分别为70.04%、60.76%和65.04%,1、2和3组的AUC值分别为0.92、0.74和0.81。总体准确度为67.69%,微观平均AUC为0.83,宏观平均AUC为0.82。结论脉搏特征的差异反映了健康人、无缺血性脑卒中史的冠心病患者和有缺血性脑卒中史的冠心病患者在动脉顺应性、外周阻力、心脏后负荷和脉搏信号复杂性方面的差异。所开发的基于脉冲的识别模型具有区分这三组的潜力,为临床实践提供了新的诊断参考。
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引用次数: 0
A Rumsfeld Matrix test for acupuncture clinical trials 针灸临床试验的拉姆斯菲尔德矩阵试验
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.001
Gong Changzhen
This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials, particularly those published in leading medical journals such as The Journal of the American Medical Association (JAMA), British Medical Journal (BMJ), The Lancet, and The New England Journal of Medicine (NEJM). The integration of randomized clinical trials (RCTs) has introduced a level of academic rigor to acupuncture research, challenging the classical deterministic model and revealing a complex landscape of known knowns, known unknowns, unknown knowns, and unknown unknowns. While RCTs have validated acupuncture’s efficacy in certain conditions, they have also highlighted considerable challenges, including the limitations of control group designs and the potential influence of placebo effects. The recurring issue of no significant differences between real and sham acupuncture in many studies underscores the need for refined control strategies and a more nuanced understanding of acupuncture’s mechanisms. This investigation calls for continued rigorous research to fully explore acupuncture’s therapeutic potential and its integration into evidence-based medicine, ultimately contributing to improved patient care and broader acceptance within the medical community.
本研究考察了拉姆斯菲尔德矩阵在针灸临床试验中的应用,特别是那些发表在《美国医学会杂志》(JAMA)、《英国医学杂志》(BMJ)、《柳叶刀》和《新英格兰医学杂志》(NEJM)等主要医学期刊上的研究。随机临床试验(rct)的整合为针灸研究引入了一定程度的学术严谨性,挑战了经典的确定性模型,揭示了已知已知、已知未知、未知已知和未知未知的复杂景观。虽然随机对照试验已经证实了针灸在某些情况下的疗效,但它们也强调了相当大的挑战,包括对照组设计的局限性和安慰剂效应的潜在影响。在许多研究中,真实针灸和假针灸之间没有显著差异的反复出现的问题强调了对精细控制策略和对针灸机制更细致的理解的需要。这项调查需要继续进行严格的研究,以充分探索针灸的治疗潜力,并将其纳入循证医学,最终为改善患者护理和在医学界得到更广泛的接受做出贡献。
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引用次数: 0
A novel method for integrating chromatographic fingerprint analytical units of Chinese materia medica: the matching frequency statistical moment method 一种整合中药材色谱指纹分析单元的新方法:匹配频率统计矩法
Q3 Medicine Pub Date : 2024-09-01 Epub Date: 2024-12-30 DOI: 10.1016/j.dcmed.2024.12.009
Haiying Li , Xue Pan , Mincun Wang , Wenjiao Li , Peng He , Sheng Huang , Fuyuan He
<div><h3>Objective</h3><div>To facilitate the quality evaluation suitable for the unique characteristics of Chinese materia medica (CMM) by developing and implementing a novel approach known as the matching frequency statistical moment (MFSM) method.</div></div><div><h3>Methods</h3><div>This study established the MFSM method. To demonstrate its effectiveness, we applied this novel approach to analyze Danxi Granules (丹膝颗粒, DXG) and its constituent herbal materials. To begin with, the ultra-performance liquid chromatography (UPLC) was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materials. Next, the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units. Then, we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment (TQSM) parameters, information entropy and information amount, along with their relative standard deviation (RSD). Finally, we compared the TQSM parameters, information entropy and information amount, and their RSD between the traditional and novel fingerprints to validate the new analytical method.</div></div><div><h3>Results</h3><div>The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method. Before integration, the ranges of the peak number, three TQSM parameters, information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07 − 209.73, <styled-content style-type="number">9390</styled-content> − <styled-content style-type="number">183064</styled-content> μv·s, 5.928 − 21.33 min, 22.62 − 106.69 min<sup>2</sup>, 4.230 − 6.539, and <styled-content style-type="number">50530</styled-content> − <styled-content style-type="number">974186</styled-content> μv·s, respectively. After integration, the ranges of these parameters were 10.00 − 88.00, <styled-content style-type="number">9390</styled-content> − <styled-content style-type="number">183064</styled-content> μv·s, 5.951 − 22.02 min, 22.27 − 104.73 min<sup>2</sup>, 2.223 − 5.277, and <styled-content style-type="number">38159</styled-content> − <styled-content style-type="number">807200</styled-content> μv·s, respectively. Correspondingly, the RSD of all the aforementioned parameters before integration were 2.12% − 9.15%, 6.04% − 49.78%, 1.15% − 23.10%, 3.97% − 25.79%, 1.49% − 19.86%, and 6.64% − 51.20%, respectively. However, after integration, they changed to 0.00%, 6.04% − 49.87%, 1.73% − 23.02%, 3.84% − 26.85%, 1.17% − 16.54%, and 6.40% − 48.59%, respectively. The results demonstrated that in the newly integrated fingerprint, the analytical units of constituent herbal materials, information entropy and information amount were significantly reduced (<em>P</em> < 0.05), wh
目的建立并实施匹配频率统计矩(MFSM)方法,为中药材质量评价提供依据。方法建立MFSM方法。为了证明其有效性,我们应用这种新方法分析了丹西颗粒(,DXG)及其成分。首先,采用超高效液相色谱法(UPLC)获得了DXG及其成分药材的色谱指纹图谱。接下来,利用MFSM压缩并将它们集成到具有更少分析单元的新指纹中。然后,我们通过计算总量子统计矩(TQSM)参数、信息熵和信息量及其相对标准偏差(RSD)来表征原始指纹和集成指纹的性质和变异性。最后,比较了传统指纹和新型指纹的TQSM参数、信息熵和信息量及其RSD,验证了新方法的有效性。结果用MFSM方法对DXG及其12种原料药的色谱峰进行了划分和整合。整合前,DXG及其12种原料药UPLC指纹图谱各峰或峰族的峰数、3个TQSM参数、信息熵和信息量的取值范围为95.07−209.73,< style-type=“number”> 990 </style -content>;−<style -content style-type="number">183064<;μv·s, 5.928−21.33分钟,22.62−106.69分钟2,4.230−6.539,和>; style- content style-type="number">50530</style -content>;−<style -content style-type="number">;分别μv·s。整合后,这些参数的取值范围为10.00 - 88.00,<style -content style-type="number">9390</style -content>;−<style -content style-type="number">183064<;μv·s, 5.951−22.02分钟,22.27−104.73分钟,2.223−5.277,和>; style- content style-type="number">38159</style -content>;−<style -content style-type="number">;分别μv·s。相应的,上述各参数积分前的RSD分别为2.12% ~ 9.15%、6.04% ~ 49.78%、1.15% ~ 23.10%、3.97% ~ 25.79%、1.49% ~ 19.86%、6.64% ~ 51.20%。整合后分别为0.00%、6.04% ~ 49.87%、1.73% ~ 23.02%、3.84% ~ 26.85%、1.17% ~ 16.54%和6.40% ~ 48.59%。结果表明,在新整合的指纹图谱中,药材成分的分析单位、信息熵和信息量均显著降低(P <;0.05), TQSM参数保持不变(P >;0.05)。此外,TQSM参数、信息熵和信息量的RSD在整合前后无显著差异(P >;0.05),但综合分析单元数量和面积的RSD显著降低(P <;0.05)。结论MFSM方法可以减少药材成分的分析单位,同时保持药材的性质和与原始指纹图谱的可变性。因此,它可以作为一种可行和可靠的工具,以减少在三坐标测量机中分析多组分的困难,促进其质量评价。
{"title":"A novel method for integrating chromatographic fingerprint analytical units of Chinese materia medica: the matching frequency statistical moment method","authors":"Haiying Li ,&nbsp;Xue Pan ,&nbsp;Mincun Wang ,&nbsp;Wenjiao Li ,&nbsp;Peng He ,&nbsp;Sheng Huang ,&nbsp;Fuyuan He","doi":"10.1016/j.dcmed.2024.12.009","DOIUrl":"10.1016/j.dcmed.2024.12.009","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To facilitate the quality evaluation suitable for the unique characteristics of Chinese materia medica (CMM) by developing and implementing a novel approach known as the matching frequency statistical moment (MFSM) method.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This study established the MFSM method. To demonstrate its effectiveness, we applied this novel approach to analyze Danxi Granules (丹膝颗粒, DXG) and its constituent herbal materials. To begin with, the ultra-performance liquid chromatography (UPLC) was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materials. Next, the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units. Then, we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment (TQSM) parameters, information entropy and information amount, along with their relative standard deviation (RSD). Finally, we compared the TQSM parameters, information entropy and information amount, and their RSD between the traditional and novel fingerprints to validate the new analytical method.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method. Before integration, the ranges of the peak number, three TQSM parameters, information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07 − 209.73, &lt;styled-content style-type=\"number\"&gt;9390&lt;/styled-content&gt; − &lt;styled-content style-type=\"number\"&gt;183064&lt;/styled-content&gt; μv·s, 5.928 − 21.33 min, 22.62 − 106.69 min&lt;sup&gt;2&lt;/sup&gt;, 4.230 − 6.539, and &lt;styled-content style-type=\"number\"&gt;50530&lt;/styled-content&gt; − &lt;styled-content style-type=\"number\"&gt;974186&lt;/styled-content&gt; μv·s, respectively. After integration, the ranges of these parameters were 10.00 − 88.00, &lt;styled-content style-type=\"number\"&gt;9390&lt;/styled-content&gt; − &lt;styled-content style-type=\"number\"&gt;183064&lt;/styled-content&gt; μv·s, 5.951 − 22.02 min, 22.27 − 104.73 min&lt;sup&gt;2&lt;/sup&gt;, 2.223 − 5.277, and &lt;styled-content style-type=\"number\"&gt;38159&lt;/styled-content&gt; − &lt;styled-content style-type=\"number\"&gt;807200&lt;/styled-content&gt; μv·s, respectively. Correspondingly, the RSD of all the aforementioned parameters before integration were 2.12% − 9.15%, 6.04% − 49.78%, 1.15% − 23.10%, 3.97% − 25.79%, 1.49% − 19.86%, and 6.64% − 51.20%, respectively. However, after integration, they changed to 0.00%, 6.04% − 49.87%, 1.73% − 23.02%, 3.84% − 26.85%, 1.17% − 16.54%, and 6.40% − 48.59%, respectively. The results demonstrated that in the newly integrated fingerprint, the analytical units of constituent herbal materials, information entropy and information amount were significantly reduced (&lt;em&gt;P&lt;/em&gt; &lt; 0.05), wh","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 294-308"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143203672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques 基于分子对接技术的挥发油成分与皮肤脂质相互作用研究
Q3 Medicine Pub Date : 2024-06-01 Epub Date: 2024-11-01 DOI: 10.1016/j.dcmed.2024.09.006
Weishuo Ren , Tuya Wulan , Xingxing Dai , Yingying Zhang , Mingyue Jia , Minfang Feng , Xinyuan Shi
<div><h3>Objective</h3><div>To analyze the interactions between different structural types of volatile oil components (VOCs) and skin lipid molecules, and investigate the mechanism of volatile oil in Chinese materia medica (VOCMM) as penetration enhancers.</div></div><div><h3>Methods</h3><div>In this study, 210 different structural types of VOCs were selected from the VOCMM penetration enhancer database, and the molecular docking experiments were conducted with three main lipid molecules of skin: ceramide 2 (CER2), cholesterol (CHL), and free fatty acid (FFA). Each VOC was docked individually with each lipid molecule. Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular structures. Nine specific pathogen-free (SPF) Sprague Dawley (SD) rats were randomly divided into Control, Nootkatone, and 3-Butylidenephthalide groups for <em>in vitro</em> percutaneous experiments, with three rats in each group. The donor pool solutions were 3% gastrodin, 3% gastrodin + 3% nootkatone, and 3% gastrodin + 3% 3-butylidenephthalide, respectively. The penetration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin (<em>Q</em><sub>12</sub>, μg/cm<sup>2</sup>).</div></div><div><h3>Results</h3><div>(i) Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA, and hydrogen bonded to the head group of CER2. Among them, sesquiterpene oxides showed the most pronounced binding affinity to CER2. The VOCs with 2 − 4 rings (including carbon rings, benzene rings, and heterocycles) demonstrated stronger binding affinity for three skin lipid molecules compared with the VOCs without intramolecular rings (<em>P</em> < 0.01). (ii) According to the cluster analysis, most of the VOCs that bond well to CER2 had 2 − 3 intramolecular rings. The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner. The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding. (iii) The results of Franz diffusion cell experiment showed that the <em>Q</em><sub>12</sub> of Control group was 260.60 ± 25.09 μg/cm<sup>2</sup>, and the transdermal absorption of gastrodin was significantly increased in Nootkatone group (<em>Q</em><sub>12</sub> = <styled-content style-type="number">5503.00</styled-content> ± <styled-content style-type="number">1080.00</styled-content> μg/cm<sup>2</sup>, <em>P</em> < 0.01). The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group (<em>Q</em><sub>12</sub> = 495.40 ± 56.98 μg/cm<sup>2</sup>, <em>P</em> > 0.05). (iv) The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.</div></div><div><h3>Conclusion</h3><div>The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the mol
目的分析不同结构类型的挥发油成分(VOCs)与皮肤脂质分子之间的相互作用,探讨中药挥发油(VOCMM)作为渗透促进剂的机理。方法本研究从VOCMM渗透促进剂数据库中筛选出210种不同结构类型的VOCs,并与皮肤的三种主要脂质分子:神经酰胺2(CER2)、胆固醇(CHL)和游离脂肪酸(FFA)进行了分子对接实验。每种挥发性有机化合物都分别与每种脂质分子进行了对接。聚类分析用于探索挥发性有机化合物的结合能与其分子结构之间的关系。九只无特定病原体(SPF)的 Sprague Dawley(SD)大鼠被随机分为对照组、诺特卡通组和 3-亚丁基酞胺组进行体外经皮实验,每组三只。供体池溶液分别为 3% 天麻素、3% 天麻素 + 3% 诺特卡酮和 3% 天麻素 + 3% 亚丁基酞。结果(i) 大多数挥发性有机化合物与 CHL 和 FFA 的疏水部分非氢键结合,与 CER2 的头部基团氢键结合。其中,倍半萜氧化物与 CER2 的结合亲和力最强。与无分子内环的挥发性有机化合物相比,具有 2 - 4 个环(包括碳环、苯环和杂环)的挥发性有机化合物与三种皮肤脂质分子的结合亲和力更强(P < 0.01)。(ii) 根据聚类分析,大多数与 CER2 结合良好的挥发性有机化合物都有 2 - 3 个分子内环。非含氧挥发性有机化合物以疏水方式与 CER2 结合。含氧挥发性有机化合物大多通过氢键与 CER2 结合。(iii) 弗兰茨扩散池实验结果表明,对照组的 Q12 为 260.60 ± 25.09 μg/cm2,而诺卡通组的胃泌素透皮吸收率显著增加(Q12 = <styled-content style-type="number">5503.00</styled-content> ± <styled-content style-type="number">1080.00</styled-content> μg/cm2,P < 0.01)。3-Butylidenephthalide 组对胃泌素的透皮吸收也有所增加(Q12 = 495.40 ± 56.98 μg/cm2,P > 0.05)。(iv) VOC 中含氧官能团的类型也是与 CER2 结合亲和力的一个影响因素。该研究为筛选挥发性油基渗透增强剂提供了理论指导和数据支持,并为研究挥发性油的渗透增强机理提供了一种简单快速的方法。
{"title":"Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques","authors":"Weishuo Ren ,&nbsp;Tuya Wulan ,&nbsp;Xingxing Dai ,&nbsp;Yingying Zhang ,&nbsp;Mingyue Jia ,&nbsp;Minfang Feng ,&nbsp;Xinyuan Shi","doi":"10.1016/j.dcmed.2024.09.006","DOIUrl":"10.1016/j.dcmed.2024.09.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To analyze the interactions between different structural types of volatile oil components (VOCs) and skin lipid molecules, and investigate the mechanism of volatile oil in Chinese materia medica (VOCMM) as penetration enhancers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, 210 different structural types of VOCs were selected from the VOCMM penetration enhancer database, and the molecular docking experiments were conducted with three main lipid molecules of skin: ceramide 2 (CER2), cholesterol (CHL), and free fatty acid (FFA). Each VOC was docked individually with each lipid molecule. Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular structures. Nine specific pathogen-free (SPF) Sprague Dawley (SD) rats were randomly divided into Control, Nootkatone, and 3-Butylidenephthalide groups for &lt;em&gt;in vitro&lt;/em&gt; percutaneous experiments, with three rats in each group. The donor pool solutions were 3% gastrodin, 3% gastrodin + 3% nootkatone, and 3% gastrodin + 3% 3-butylidenephthalide, respectively. The penetration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin (&lt;em&gt;Q&lt;/em&gt;&lt;sub&gt;12&lt;/sub&gt;, μg/cm&lt;sup&gt;2&lt;/sup&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;(i) Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA, and hydrogen bonded to the head group of CER2. Among them, sesquiterpene oxides showed the most pronounced binding affinity to CER2. The VOCs with 2 − 4 rings (including carbon rings, benzene rings, and heterocycles) demonstrated stronger binding affinity for three skin lipid molecules compared with the VOCs without intramolecular rings (&lt;em&gt;P&lt;/em&gt; &lt; 0.01). (ii) According to the cluster analysis, most of the VOCs that bond well to CER2 had 2 − 3 intramolecular rings. The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner. The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding. (iii) The results of Franz diffusion cell experiment showed that the &lt;em&gt;Q&lt;/em&gt;&lt;sub&gt;12&lt;/sub&gt; of Control group was 260.60 ± 25.09 μg/cm&lt;sup&gt;2&lt;/sup&gt;, and the transdermal absorption of gastrodin was significantly increased in Nootkatone group (&lt;em&gt;Q&lt;/em&gt;&lt;sub&gt;12&lt;/sub&gt; = &lt;styled-content style-type=\"number\"&gt;5503.00&lt;/styled-content&gt; ± &lt;styled-content style-type=\"number\"&gt;1080.00&lt;/styled-content&gt; μg/cm&lt;sup&gt;2&lt;/sup&gt;, &lt;em&gt;P&lt;/em&gt; &lt; 0.01). The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group (&lt;em&gt;Q&lt;/em&gt;&lt;sub&gt;12&lt;/sub&gt; = 495.40 ± 56.98 μg/cm&lt;sup&gt;2&lt;/sup&gt;, &lt;em&gt;P&lt;/em&gt; &gt; 0.05). (iv) The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the mol","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 2","pages":"Pages 148-159"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis 揭示生物活性柚皮苷对地塞米松诱导的骨质疏松症大鼠的骨质保护潜力
Q3 Medicine Pub Date : 2024-06-01 Epub Date: 2024-11-01 DOI: 10.1016/j.dcmed.2024.09.008
Tejal R. Waykar, Satish K. Mandlik, Deepa S. Mandlik
<div><h3>Objective</h3><div>To investigate the protective effects of naringenin (NRG) against dexamethasone (DEX)-induced osteoporosis (OP) in rats.</div></div><div><h3>Methods</h3><div>Molecular docking of NRG was done with AutoDock Vina 1.2.0 software. Forty-eight female Wistar rats were randomly divided into six groups (<em>n</em> = 8 each): normal control (NC), DEX (7 mg/kg, i.m.), NRG-low (NRG-L; 25 mg/kg, i.g.), NRG-medium (NRG-M; 50 mg/kg, i.g.), NRG-high (NRG-H; 100 mg/kg, i.g.), and alendronate (ALN; 0.25 mg/d, i.g.) groups. OP was induced by administering DEX once a week for five weeks in all groups except NC group. Begining in the third week after the initial DEX administration, the rats in NRG-L, NRG-M, NRG-H, and ALN groups received the corresponding treatments daily for three weeks, while NC and DEX groups received no additional treatment. Serum samples were collected at the end of the experiment for biochemical, bone turnover, antioxidant, lipid profile, and inflammatory cytokine analyses. Femur bones underwent physical parameter testing and histopathological examination.</div></div><div><h3>Results</h3><div>The molecular docking results illustrated that NRG docked with calcitonin (CT), low-density lipoprotein (LDL), bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF) receptor, forkhead transcription factors, and osteoprogenitor cells showed good binding energy. In rats administered with 25, 50, and 100 mg/kg NRG, there was a significant enhancement in serum biochemical indices, characterized by a reduction in tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and an elevation in osteocalcin (OC) and CT levels (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.001, respectively). Despite no significant changes in thickness, weight, and length (<em>P</em> > 0.05), there was a marked increase in bone mineral density (BMD) (<em>P</em> < 0.01, <em>P</em> < 0.001, and <em>P</em> < 0.001, respectively). Antioxidant enzyme markers showed significant upregulation, with higher glutathione, superoxide dismutase, and catalase, and a concurrent decrease in malondialdehyde (MDA) (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.001, respectively). The lipid profile also improved significantly, with lower cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL) levels, and an increase in high-density lipoprotein (HDL) level (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.001, respectively). Inflammatory cytokine levels were reduced, as evidenced by decreases in tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1<em>β</em> (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.001, respectively). Furthermore, histological alterations revealed obvious improvements, and the body weight of rats treated with NRG showed an increase compared with DEX group.</div></div><div><h3>Conclusion</h3><div>These findings im
目的 研究柚皮苷(NRG)对地塞米松(DEX)诱导的大鼠骨质疏松症(OP)的保护作用。 方法 使用 AutoDock Vina 1.2.0 软件对 NRG 进行分子对接。将48只雌性Wistar大鼠随机分为6组(每组8只):正常对照组(NC)、DEX组(7 mg/kg,静注)、NRG-低(NRG-L;25 mg/kg,静注)、NRG-中(NRG-M;50 mg/kg,静注)、NRG-高(NRG-H;100 mg/kg,静注)和阿仑膦酸钠组(ALN;0.25 mg/d,静注)。除NC组外,其他各组均通过每周一次的DEX诱导OP,为期五周。从首次给予 DEX 后的第三周开始,NRG-L 组、NRG-M 组、NRG-H 组和 ALN 组的大鼠每天接受相应的治疗,持续三周,而 NC 组和 DEX 组不接受额外的治疗。实验结束时收集血清样本,进行生化、骨转换、抗氧化、血脂和炎症细胞因子分析。结果分子对接结果表明,NRG 与降钙素(CT)、低密度脂蛋白(LDL)、骨形态发生蛋白(BMP)、血管内皮生长因子(VEGF)受体、叉头转录因子和骨生成细胞的对接显示出良好的结合能。大鼠服用 25、50 和 100 毫克/千克 NRG 后,血清生化指标显著提高,其特征是抗酒石酸磷酸酶(TRAP)和甲状旁腺激素(PTH)降低,骨钙素(OC)和 CT 水平升高(分别为 P <0.05、P <0.01 和 P <0.001)。尽管厚度、重量和长度没有明显变化(P> 0.05),但骨矿物质密度(BMD)明显增加(分别为 P < 0.01、P < 0.001 和 P < 0.001)。抗氧化酶标记物显示出明显的上调,谷胱甘肽、超氧化物歧化酶和过氧化氢酶升高,丙二醛(MDA)同时下降(分别为 P <0.05、P <0.01 和 P <0.001)。血脂状况也有明显改善,胆固醇(CH)、甘油三酯(TG)和低密度脂蛋白(LDL)水平降低,高密度脂蛋白(HDL)水平升高(分别为 P <0.05、P <0.01 和 P <0.001)。炎症细胞因子水平降低,表现为肿瘤坏死因子(TNF)、白细胞介素(IL)-6 和 IL-1β 的下降(分别为 P < 0.05、P < 0.01 和 P < 0.001)。结论这些研究结果表明,NRG 对 DEX 诱导的大鼠 OP 具有保护作用,因为它能通过增加骨转换标志物(包括 OC 和 CT)的数量、恢复抗氧化状态、脂质代谢和炎症标志物来促进骨形成过程。
{"title":"Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis","authors":"Tejal R. Waykar,&nbsp;Satish K. Mandlik,&nbsp;Deepa S. Mandlik","doi":"10.1016/j.dcmed.2024.09.008","DOIUrl":"10.1016/j.dcmed.2024.09.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate the protective effects of naringenin (NRG) against dexamethasone (DEX)-induced osteoporosis (OP) in rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Molecular docking of NRG was done with AutoDock Vina 1.2.0 software. Forty-eight female Wistar rats were randomly divided into six groups (&lt;em&gt;n&lt;/em&gt; = 8 each): normal control (NC), DEX (7 mg/kg, i.m.), NRG-low (NRG-L; 25 mg/kg, i.g.), NRG-medium (NRG-M; 50 mg/kg, i.g.), NRG-high (NRG-H; 100 mg/kg, i.g.), and alendronate (ALN; 0.25 mg/d, i.g.) groups. OP was induced by administering DEX once a week for five weeks in all groups except NC group. Begining in the third week after the initial DEX administration, the rats in NRG-L, NRG-M, NRG-H, and ALN groups received the corresponding treatments daily for three weeks, while NC and DEX groups received no additional treatment. Serum samples were collected at the end of the experiment for biochemical, bone turnover, antioxidant, lipid profile, and inflammatory cytokine analyses. Femur bones underwent physical parameter testing and histopathological examination.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The molecular docking results illustrated that NRG docked with calcitonin (CT), low-density lipoprotein (LDL), bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF) receptor, forkhead transcription factors, and osteoprogenitor cells showed good binding energy. In rats administered with 25, 50, and 100 mg/kg NRG, there was a significant enhancement in serum biochemical indices, characterized by a reduction in tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and an elevation in osteocalcin (OC) and CT levels (&lt;em&gt;P&lt;/em&gt; &lt; 0.05, &lt;em&gt;P&lt;/em&gt; &lt; 0.01, and &lt;em&gt;P&lt;/em&gt; &lt; 0.001, respectively). Despite no significant changes in thickness, weight, and length (&lt;em&gt;P&lt;/em&gt; &gt; 0.05), there was a marked increase in bone mineral density (BMD) (&lt;em&gt;P&lt;/em&gt; &lt; 0.01, &lt;em&gt;P&lt;/em&gt; &lt; 0.001, and &lt;em&gt;P&lt;/em&gt; &lt; 0.001, respectively). Antioxidant enzyme markers showed significant upregulation, with higher glutathione, superoxide dismutase, and catalase, and a concurrent decrease in malondialdehyde (MDA) (&lt;em&gt;P&lt;/em&gt; &lt; 0.05, &lt;em&gt;P&lt;/em&gt; &lt; 0.01, and &lt;em&gt;P&lt;/em&gt; &lt; 0.001, respectively). The lipid profile also improved significantly, with lower cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL) levels, and an increase in high-density lipoprotein (HDL) level (&lt;em&gt;P&lt;/em&gt; &lt; 0.05, &lt;em&gt;P&lt;/em&gt; &lt; 0.01, and &lt;em&gt;P&lt;/em&gt; &lt; 0.001, respectively). Inflammatory cytokine levels were reduced, as evidenced by decreases in tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1&lt;em&gt;β&lt;/em&gt; (&lt;em&gt;P&lt;/em&gt; &lt; 0.05, &lt;em&gt;P&lt;/em&gt; &lt; 0.01, and &lt;em&gt;P&lt;/em&gt; &lt; 0.001, respectively). Furthermore, histological alterations revealed obvious improvements, and the body weight of rats treated with NRG showed an increase compared with DEX group.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings im","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 2","pages":"Pages 171-183"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An interpretability model for syndrome differentiation of HBV-ACLF in traditional Chinese medicine using small-sample imbalanced data 利用小样本不平衡数据建立中药 HBV-ACLF 证候区分的可解释性模型
Q3 Medicine Pub Date : 2024-06-01 Epub Date: 2024-11-01 DOI: 10.1016/j.dcmed.2024.09.005
Zhou Zhan , Peng Qinghua , Xiao Xiaoxia , Zou Beiji , Liu Bin , Guo Shuixia
<div><h3>Objective</h3><div>Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) generally have small sample sizes and a class imbalance. However, most machine learning models are designed based on balanced data and lack interpretability. This study aimed to propose a traditional Chinese medicine (TCM) diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory, which is clinically interpretable and highly accurate.</div></div><div><h3>Methods</h3><div>We collected medical records from 261 patients diagnosed with HBV-ACLF, including three syndromes: Yang jaundice (214 cases), Yang-Yin jaundice (41 cases), and Yin jaundice (6 cases). To avoid overfitting of the machine learning model, we excluded the cases of Yin jaundice. After data standardization and cleaning, we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice. To address the class imbalance issue, we employed the oversampling method and five machine learning methods, including logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost) to construct the syndrome diagnosis models. This study used precision, F1 score, the area under the receiver operating characteristic (ROC) curve (AUC), and accuracy as model evaluation metrics. The model with the best classification performance was selected to extract the diagnostic rule, and its clinical significance was thoroughly analyzed. Furthermore, we proposed a novel multiple-round stable rule extraction (MRSRE) method to obtain a stable rule set of features that can exhibit the model’s clinical interpretability.</div></div><div><h3>Results</h3><div>The precision of the five machine learning models built using oversampled balanced data exceeded 0.90. Among these models, the accuracy of RF classification of syndrome types was 0.92, and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaundice were 0.93 and 0.94, respectively. Additionally, the AUC was 0.98. The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the common features of Yang jaundice and Yang-Yin jaundice were wiry pulse, yellowing of the urine, skin, and eyes, normal tongue body, healthy sublingual vessel, nausea, oil loathing, and poor appetite. The main features of Yang jaundice were a red tongue body and thickened sublingual vessels, whereas those of Yang-Yin jaundice were a dark tongue body, pale white tongue body, white tongue coating, lack of strength, slippery pulse, light red tongue body, slimy tongue coating, and abdominal distension. This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory.</div></div><div><h3>Conclusion</h3><div>Our model can be utilized for differentiating HBV-ACLF syndromes, which has the potential to be applied to generate other clinically i
目标与乙型肝炎相关的急性慢性肝衰竭(HBV-ACLF)相关的临床病历数据通常样本量较小,且存在类别不平衡的问题。然而,大多数机器学习模型都是基于平衡数据设计的,缺乏可解释性。本研究旨在提出一种基于中医辨证论治理论的 HBV-ACLF 中医诊断模型,该模型具有临床可解释性和高准确性:阳黄(214 例)、阳阴黄(41 例)和阴黄(6 例)。为了避免机器学习模型的过度拟合,我们排除了阴性黄疸的病例。经过数据标准化和清理后,我们获得了 255 份阳黄疸和阳阴黄疸的相关病历。为了解决类不平衡问题,我们采用了超采样方法和五种机器学习方法,包括逻辑回归(LR)、支持向量机(SVM)、决策树(DT)、随机森林(RF)和极梯度提升(XGBoost),来构建综合征诊断模型。本研究采用精确度、F1得分、接收者操作特征曲线下面积(AUC)和准确度作为模型评价指标。选择分类性能最佳的模型提取诊断规则,并深入分析其临床意义。此外,我们还提出了一种新颖的多轮稳定规则提取(MRSRE)方法,以获得稳定的规则特征集,从而展现模型的临床可解释性。在这些模型中,综合征类型 RF 分类的准确率为 0.92,而阳黄疸和阳阴黄疸两个类别的平均 F1 分数分别为 0.93 和 0.94。此外,AUC 为 0.98。基于 MRSRE 方法的射频综合征分型模型的提取规则显示,阳黄疸和阳阴黄疸的共同特征是脉细数,尿黄、肤黄、目黄,舌体正常,舌下血管健康,恶心、厌油、食欲不振。阳黄疸的主要特征是舌体红,舌下血管增粗,而阳阴黄疸的主要特征是舌体暗、舌体淡白、舌苔白、乏力、脉滑、舌体淡红、舌苔黏腻、腹胀。结论我们的模型可用于鉴别 HBV-ACLF 综合征,并有可能应用于生成其他临床可解释模型,在样本量较小且类群不平衡的临床数据上具有较高的准确性。
{"title":"An interpretability model for syndrome differentiation of HBV-ACLF in traditional Chinese medicine using small-sample imbalanced data","authors":"Zhou Zhan ,&nbsp;Peng Qinghua ,&nbsp;Xiao Xiaoxia ,&nbsp;Zou Beiji ,&nbsp;Liu Bin ,&nbsp;Guo Shuixia","doi":"10.1016/j.dcmed.2024.09.005","DOIUrl":"10.1016/j.dcmed.2024.09.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) generally have small sample sizes and a class imbalance. However, most machine learning models are designed based on balanced data and lack interpretability. This study aimed to propose a traditional Chinese medicine (TCM) diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory, which is clinically interpretable and highly accurate.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We collected medical records from 261 patients diagnosed with HBV-ACLF, including three syndromes: Yang jaundice (214 cases), Yang-Yin jaundice (41 cases), and Yin jaundice (6 cases). To avoid overfitting of the machine learning model, we excluded the cases of Yin jaundice. After data standardization and cleaning, we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice. To address the class imbalance issue, we employed the oversampling method and five machine learning methods, including logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost) to construct the syndrome diagnosis models. This study used precision, F1 score, the area under the receiver operating characteristic (ROC) curve (AUC), and accuracy as model evaluation metrics. The model with the best classification performance was selected to extract the diagnostic rule, and its clinical significance was thoroughly analyzed. Furthermore, we proposed a novel multiple-round stable rule extraction (MRSRE) method to obtain a stable rule set of features that can exhibit the model’s clinical interpretability.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The precision of the five machine learning models built using oversampled balanced data exceeded 0.90. Among these models, the accuracy of RF classification of syndrome types was 0.92, and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaundice were 0.93 and 0.94, respectively. Additionally, the AUC was 0.98. The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the common features of Yang jaundice and Yang-Yin jaundice were wiry pulse, yellowing of the urine, skin, and eyes, normal tongue body, healthy sublingual vessel, nausea, oil loathing, and poor appetite. The main features of Yang jaundice were a red tongue body and thickened sublingual vessels, whereas those of Yang-Yin jaundice were a dark tongue body, pale white tongue body, white tongue coating, lack of strength, slippery pulse, light red tongue body, slimy tongue coating, and abdominal distension. This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our model can be utilized for differentiating HBV-ACLF syndromes, which has the potential to be applied to generate other clinically i","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 2","pages":"Pages 137-147"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway 左归姜汤解郁方通过抑制JNK信号通路改善糖尿病抑郁大鼠海马神经元凋亡
Q3 Medicine Pub Date : 2024-06-01 Epub Date: 2024-11-01 DOI: 10.1016/j.dcmed.2024.09.010
Zhao Hongqing , Mou Qingrui , Jiang Jiaqi , Zhu Xuan , Liu Zhuo , Wang Yuhong
<div><h3>Objective</h3><div>To investigate the effect of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZJJF) on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.</div></div><div><h3>Methods</h3><div>(i) A total of 72 specific pathogen-free (SPF) grade male Sprague Dawley (SD) rats were randomly divided into six groups, with 12 rats in each group: control, model, metformin (Met, 0.18 g/kg) + fluoxetine (Flu, 1.8 mg/kg), and the high-, medium-, and low-ZJJF dosages (ZJJF-H, 20.52 g/kg; ZJJF-M, 10.26 g/kg; ZJJF-L, 5.13 g/kg) groups. All groups except control group were injected once via the tail vein with streptozotocin (STZ, 38 mg/kg) combined with 28 d of chronic unpredictable mild stress (CUMS) to establish diabetic rat models with depression. During the CUMS modeling period, treatments were administered via gavage, with control and model groups receiving an equivalent volume of distilled water for 28 d. The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose, insulin, and glycated hemoglobin levels, along with behavioral assessments, including the open field test (OFT), forced swim test (FST), and sucrose preference test (SPT). Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Apoptosis-related proteins Bax, Bcl-2, caspase-3, and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). (ii) To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF, an additional 50 SPF grade male SD rats were randomly divided into five groups, with 10 rats in each group: control, model, SP600125 (SP6, a JNK antagonist, 10 mg/kg), ZJJF (20.52 g/kg), and ZJJF (20.52 g/kg) + Anisomycin (Aniso, a JNK agonist, 15 mg/kg) groups. Except for control group, all groups were established as diabetic rat models with depression, and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period. Behavioral changes in rats were evaluated through the OFT, FST, and SPT, and hippocampal neuron damage and apoptosis were observed using HE staining, Nissl staining, TUNEL staining, and transmission electron microscopy (TEM). Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.</div></div><div><h3>Results</h3><div>(i) ZJJF significantly reduced the high blood glucose, insulin, and glycated hemoglobin levels in model rats (<em>P</em> < 0.01). It increased autonomous activity and decreased despair-like behaviors (<em>P</em> < 0.01), improved the pathological damage of hippocam
目的 研究左归降糖解郁方对糖尿病伴抑郁大鼠海马神经元凋亡的影响,并探讨其机制是否涉及JNK信号通路的调控。方法(i)将72只无特定病原体(SPF)级雄性Sprague Dawley(SD)大鼠随机分为6组,每组12只,分别为对照组、模型组、二甲双胍(Met,0.18 g/kg)+氟西汀(Flu,1.8 mg/kg)组、ZJJF高、中、低剂量组(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)。除对照组外,其他各组均经尾部静脉注射一次链脲佐菌素(STZ,38 mg/kg),并给予28 d的慢性不可预知的轻度应激(CUMS),以建立糖尿病大鼠抑郁模型。通过测量空腹血糖、胰岛素和糖化血红蛋白水平,以及行为评估,包括开阔地试验(OFT)、强迫游泳试验(FST)和蔗糖偏好试验(SPT),评估了ZJJF降低血糖和缓解抑郁的功效。使用苏木精-伊红(HE)染色和末端脱氧核苷酸转移酶介导的 dUTP nick-end 标记(TUNEL)染色评估海马组织损伤和神经细胞凋亡。使用 Western 印迹和实时定量聚合酶链反应(RT-qPCR)检测凋亡相关蛋白 Bax、Bcl-2、caspase-3 和 JNK/Elk-1/c-fos 信号通路的表达水平。(ii) 为进一步阐明 JNK 信号通路在海马神经元凋亡中的作用及 ZJJF 的药理作用,将另外 50 只 SPF 级雄性 SD 大鼠随机分为 5 组,每组 10 只,分别为对照组、模型组、SP600125(SP6,一种 JNK 拮抗剂,10 mg/kg)组、ZJJF(20.52 g/kg)组、ZJJF(20.52 g/kg)+ Anisomycin(Aniso,一种 JNK 激动剂,15 mg/kg)组。除对照组外,其余各组均为糖尿病大鼠抑郁模型,在CUMS建模期间,ZJJF通过灌胃给药,SP6和Aniso通过腹腔注射给药,持续28天。通过OFT、FST和SPT评估大鼠的行为变化,并使用HE染色、Nissl染色、TUNEL染色和透射电子显微镜(TEM)观察海马神经元损伤和凋亡。结果(i) ZJJF能显著降低模型大鼠的高血糖、胰岛素和糖化血红蛋白水平(P < 0.01)。ZJJF能提高大鼠的自主活动能力,减少绝望样行为(P< 0.01),改善海马神经元的病理损伤,增加神经元核的数量(P< 0.01),减少机化细胞、空泡细胞和凋亡神经元的数量(分别为P< 0.05、P< 0.01和P< 0.01)。ZJJF 下调促凋亡蛋白 Bax 和 caspase-3 的表达水平(P <;0.01),上调抗凋亡蛋白 Bcl-2 的表达水平(P <;0.01),并显著抑制磷酸化 JNK(p-JNK)、Elk-1 和 c-fos 的过度表达(P <;0.01)。(ii) SP6 增加了模型大鼠的自主活动,减少了绝望时间(P <;0.05),但对蔗糖偏好无显著影响(P >;0.05)。它增加了海马神经元中 Nissl 体的数量(P <;0.01),降低了 Bax(P <;0.01)和 caspase-3 (P <;0.05)的蛋白表达水平,并减少了凋亡神经元的数量(P <;0.05)。SP6还能提高Bcl-2的表达水平(P <0.01),抑制p-JNK、Elk-1和c-fos的高表达水平(分别为P <0.01、P <0.01和P <0.05),表明糖尿病抑郁大鼠海马神经元凋亡与JNK信号通路的异常激活有关。与ZJJF组相比,ZJJF + Aniso组大鼠的蔗糖偏好下降(P < 0.05),绝望时间延长(P < 0.01),海马神经元损伤更为显著。该组还表现出 Bcl-2 表达水平下降(P < 0.01),Bax、caspase-3、p-JNK、Elk-1 和 c-fos 表达水平上升(P < 0.01、P < 0.05、P < 0.05、P < 0.01和P <0.05),表明ZJJF的抗抑郁作用、对神经元凋亡的改善作用以及对JNK信号分子的调控作用都可以通过特定的JNK激动剂逆转。结论ZJJF具有显著的降血糖作用,并通过抑制JNK信号通路的活化改善海马神经元的凋亡,是临床治疗糖尿病抑郁症的有效配方。
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Digital Chinese Medicine
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