Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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
{"title":"Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer’s disease model","authors":"Shan Hui , Qing Zheng , Hongli Li , Lemei Zhu , Beibei Wu , Lihui Liang , Jingjing Yang","doi":"10.1016/j.dcmed.2024.12.008","DOIUrl":"10.1016/j.dcmed.2024.12.008","url":null,"abstract":"<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","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}
Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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。
{"title":"Metabolic characteristics of Qi-Yin deficiency and heat stagnation in liver meridian patterns of dry eye based on tear metabolomics","authors":"Xie Mingxia , Cai Zengyun , Li Junyao , Tan Jiaren , Liu Pei , Yu Yanlan , Jiao Luojia","doi":"10.1016/j.dcmed.2024.12.007","DOIUrl":"10.1016/j.dcmed.2024.12.007","url":null,"abstract":"<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","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 274-283"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143262513","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}
Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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
{"title":"Construction and optimization of traditional Chinese medicine constitution prediction models based on deep learning","authors":"Zhang Xinge, Xu Qiang, Wen Chuanbiao, Luo Yue","doi":"10.1016/j.dcmed.2024.12.004","DOIUrl":"10.1016/j.dcmed.2024.12.004","url":null,"abstract":"<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 ","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 241-255"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143262723","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}
Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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.
{"title":"Analysis on pulse features of coronary heart disease patients with or without a history of ischemic stroke","authors":"Li Xin , Li Wei , Ng Man-In, Parry Natalie Ann, Li Siqi, Li Rui, Guo Rui","doi":"10.1016/j.dcmed.2024.12.006","DOIUrl":"10.1016/j.dcmed.2024.12.006","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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 MSE<sub>1</sub> – MSE<sub>7</sub> (<em>P</em> < 0.05), while Group 3 showed significant increases in pulse features T5/T4, T, H1/T1, W1, W2, AS, and Ad, and decreased in MSE<sub>1</sub> – MSE<sub>20</sub> (<em>P</em> < 0.05). Compared with Group 2, Group 3 demonstrated notable increases in H1/T1 and As (<em>P</em> < 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 264-273"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143262512","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}
Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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.
{"title":"A Rumsfeld Matrix test for acupuncture clinical trials","authors":"Gong Changzhen","doi":"10.1016/j.dcmed.2024.12.001","DOIUrl":"10.1016/j.dcmed.2024.12.001","url":null,"abstract":"<div><div>This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials, particularly those published in leading medical journals such as <em>The Journal of the American Medical Association</em> (JAMA), <em>British Medical Journal</em> (BMJ), <em>The Lancet</em>, and <em>The New England Journal of Medicine</em> (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.</div></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 3","pages":"Pages 209-223"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143262516","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}
Pub Date : 2024-09-01Epub Date: 2024-12-30DOI: 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
{"title":"A novel method for integrating chromatographic fingerprint analytical units of Chinese materia medica: the matching frequency statistical moment method","authors":"Haiying Li , Xue Pan , Mincun Wang , Wenjiao Li , Peng He , Sheng Huang , Fuyuan He","doi":"10.1016/j.dcmed.2024.12.009","DOIUrl":"10.1016/j.dcmed.2024.12.009","url":null,"abstract":"<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","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}
Pub Date : 2024-06-01Epub Date: 2024-11-01DOI: 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
{"title":"Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques","authors":"Weishuo Ren , Tuya Wulan , Xingxing Dai , Yingying Zhang , Mingyue Jia , Minfang Feng , Xinyuan Shi","doi":"10.1016/j.dcmed.2024.09.006","DOIUrl":"10.1016/j.dcmed.2024.09.006","url":null,"abstract":"<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","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}
Pub Date : 2024-06-01Epub Date: 2024-11-01DOI: 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, Satish K. Mandlik, Deepa S. Mandlik","doi":"10.1016/j.dcmed.2024.09.008","DOIUrl":"10.1016/j.dcmed.2024.09.008","url":null,"abstract":"<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","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}
Pub Date : 2024-06-01Epub Date: 2024-11-01DOI: 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
{"title":"An interpretability model for syndrome differentiation of HBV-ACLF in traditional Chinese medicine using small-sample imbalanced data","authors":"Zhou Zhan , Peng Qinghua , Xiao Xiaoxia , Zou Beiji , Liu Bin , Guo Shuixia","doi":"10.1016/j.dcmed.2024.09.005","DOIUrl":"10.1016/j.dcmed.2024.09.005","url":null,"abstract":"<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","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}
Pub Date : 2024-06-01Epub Date: 2024-11-01DOI: 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
{"title":"Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway","authors":"Zhao Hongqing , Mou Qingrui , Jiang Jiaqi , Zhu Xuan , Liu Zhuo , Wang Yuhong","doi":"10.1016/j.dcmed.2024.09.010","DOIUrl":"10.1016/j.dcmed.2024.09.010","url":null,"abstract":"<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","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":"7 2","pages":"Pages 195-208"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572462","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}