1.Exploring Therapeutic Mechanism of Xihuang Wan for Hyperplasia of Mammary Glands Based on Network Pharmacology, Molecular Docking, and Cell Experiments
Junliang WANG ; Peihua LIANG ; Xueli MA ; Juanxia SUN ; Tao HAN ; Yongmei LAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):41-49
ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology, molecular docking, and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, Therapeutic Target Database (TTD), Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0, the STRING database was used to analyze the protein-protein interactions, and Cytoscape was used for the core target analysis and visualization. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for enrichment analysis. Molecular docking was carried out in Autodock, and cell experiments were conducted to verify the prediction results. In the cell experiments, estradiol and progesterone (E2+P) were used to intervene in human mammary epithelial/MCF-10A cells, and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 (CCK-8) was used to measure the cell proliferation, and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot, respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained, from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes, which may be related to protein kinase B (Akt)-related molecular functions, estrogen signaling pathway, prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 (ESR1), serine/threonine kinase 1 (Akt1), non-receptor tyrosine kinase (SRC), and signal transducer and activator of transcription 3 (STAT3) all had strong binding activity with the nine active ingredients, suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the Janus kinase (JAK)/STAT3 signaling pathway. The results of cell experiments showed that E2+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells (P<0.05), while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E2+P (P<0.05). Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E2+P (P<0.01). The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K, Akt, JAK2, and STAT3 in MCF-10A cells treated with E2+P (P<0.01). The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K, p-Akt/Akt, p-JAK2/JAK2, and p-STAT3/STAT3 in MCF-10A cells treated with E2+P (P<0.05). ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells, which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.
2.A systematic review on the integrated application of evidence-based narrative education and undergraduate nursing teaching
Nannan BAI ; Meng LI ; Qian LIANG ; Chou YAO ; Yan WANG ; Ju HAN ; Chenyang HOU ; Nana XING
Chinese Medical Ethics 2026;39(2):229-237
ObjectiveTo systematically evaluate the application of narrative education in undergraduate nursing teaching, to understand the current application status of narrative education, and to provide a theoretical basis for the subsequent establishment of a sound narrative education system. MethodsA systematic search was conducted for studies published in Chinese and English databases on applying narrative education to undergraduate nursing teaching, with the search period ranging from database inception to February 23, 2025. Literature was screened, and relevant information was extracted. A rigorous quality evaluation was conducted on the included studies, and a descriptive analysis was performed on their content. ResultsA total of 20 papers were included, involving 3,180 research subjects, all of whom were undergraduate nursing students. The results of descriptive analysis showed that the teaching model of narrative education primarily encompassed reading narrative works, watching films and videos, performing narrative scenarios, and writing reflective journals. The course setting and content covered pre-teaching preparation and in-teaching implementation. The evaluation of teaching effectiveness included the evaluation of teachers’ teaching methods (student evaluation/self-evaluation) and the evaluation of students’ learning effectiveness (course grade evaluation/humanistic care scale/empathy scale assessment, and others). ConclusionNarrative education combines abstract concepts with concrete clinical situations, which not only enriches students’ learning experiences but also enhances their humanistic literacy. Meanwhile, it provides teachers with opportunities to develop their narrative teaching skills, which requires them to possess profound professional knowledge and employ narrative techniques to guide students in reflection and critical thinking, thereby improving teaching quality and learning outcomes. Future efforts should consistently deepen the connotation research of narrative education and build a systematic nursing education system.
3.Survey on the awareness and clinical application of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians
Yuanyuan KONG ; Yujie GUO ; Yujuan GUAN ; Xuan LIANG ; Zhongjie HU ; Xiaobo LU ; Mingqin LU ; Yongfeng YANG ; Meifang HAN ; Hong YOU ; Zhiyun YANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(6):1068-1074
ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. MethodsFrom July 19 to December 31, 2024, a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide, including their awareness and practice based on 18 questions regarding testing and referral, diagnosis and treatment, and follow-up. ResultsAmong all respondents, only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B, with an overall awareness rate of 22.0%. Only 20% — 40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy, while 80% — 100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year, 3 years, and 5 years were 67.5% 57.5% and 47.5%,respectively, showing a trend of gradual reduction, which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians, insufficient awareness of the disease among patients, and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection, diagnosis, treatment, and management” for patients with chronic hepatitis B in healthcare institutions, in order to promote the implementation of the guidelines.
4.Randomized, double-blind, parallel-controlled, multicenter, equivalence clinical trial of Jiuwei Xifeng Granules(Os Draconis replaced by Ostreae Concha) for treating tic disorder in children.
Qiu-Han CAI ; Cheng-Liang ZHONG ; Si-Yuan HU ; Xin-Min LI ; Zhi-Chun XU ; Hui CHEN ; Ying HUA ; Jun-Hong WANG ; Ji-Hong TANG ; Bing-Xiang MA ; Xiu-Xia WANG ; Ai-Zhen WANG ; Meng-Qing WANG ; Wei ZHANG ; Chun WANG ; Yi-Qun TENG ; Yi-Hui SHAN ; Sheng-Xuan GUO
China Journal of Chinese Materia Medica 2025;50(6):1699-1705
Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent
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Child
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Child, Preschool
;
Female
;
Humans
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Male
;
Double-Blind Method
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Drugs, Chinese Herbal/therapeutic use*
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Tic Disorders/drug therapy*
;
Treatment Outcome
5.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
;
Bile Acids and Salts/metabolism*
;
Animals
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Male
;
Liver/injuries*
;
Chemical and Drug Induced Liver Injury/genetics*
;
Drugs, Chinese Herbal/adverse effects*
;
Humans
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Rats, Sprague-Dawley
;
Mice
;
Rats
6.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
;
Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
;
Male
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Humans
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Cytokines/immunology*
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Female
;
Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
7.Research progress on prevention and treatment of hepatocellular carcinoma with traditional Chinese medicine based on gut microbiota.
Rui REN ; Xing YANG ; Ping-Ping REN ; Qian BI ; Bing-Zhao DU ; Qing-Yan ZHANG ; Xue-Han WANG ; Zhong-Qi JIANG ; Jin-Xiao LIANG ; Ming-Yi SHAO
China Journal of Chinese Materia Medica 2025;50(15):4190-4200
Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans
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Gastrointestinal Microbiome/drug effects*
;
Carcinoma, Hepatocellular/microbiology*
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Liver Neoplasms/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Medicine, Chinese Traditional
8.Regulatory effects of Dangua Humai Oral Liquid on gut microbiota and mucosal barrier in mice with glucolipid metabolism disorder.
Zhuang HAN ; Lin-Xi JIN ; Zhi-Ta WANG ; Liu-Qing YANG ; Liang LI ; Yi RUAN ; Qi-Wei CHEN ; Shu-Hong YAO ; Xian-Pei HENG
China Journal of Chinese Materia Medica 2025;50(15):4315-4324
The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals
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Gastrointestinal Microbiome/drug effects*
;
Mice
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Intestinal Mucosa/microbiology*
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Male
;
Drugs, Chinese Herbal/administration & dosage*
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Mice, Inbred C57BL
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Humans
;
Glycolipids/metabolism*
;
Lipid Metabolism/drug effects*
;
Administration, Oral
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Disease Models, Animal
9.Potential mechanism of Yueju Pills in improving depressive symptoms of psychocardiac diseases based on metabolomics and network pharmacology.
Cheng-Yu DU ; Xue-Feng GUO ; Han-Wen ZHANG ; Jian LIANG ; Huan ZHANG ; Guo-Wei HUANG ; Ping NI ; Hai-Jun MA ; You YU ; Rui YU
China Journal of Chinese Materia Medica 2025;50(16):4564-4573
The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals
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Network Pharmacology
;
Mice
;
Drugs, Chinese Herbal/administration & dosage*
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Metabolomics
;
Male
;
Depression/genetics*
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Humans
;
Hippocampus/drug effects*
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
10.Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.
Zhao ZHANG ; Hua JIANG ; Li HUANG ; Sixi LIU ; Xiaoya ZHOU ; Yun CAI ; Ming LI ; Fei GAO ; Xiaoting LIANG ; Kam-Sze TSANG ; Guangfu CHEN ; Chui-Yan MA ; Yuet-Hung CHAI ; Hongsheng LIU ; Chen YANG ; Mo YANG ; Xiaoling ZHANG ; Shuo HAN ; Xin DU ; Ling CHEN ; Wuh-Liang HWU ; Jiacai ZHUO ; Qizhou LIAN
Protein & Cell 2025;16(1):16-27
Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans
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Leukodystrophy, Metachromatic/genetics*
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Pilot Projects
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Genetic Therapy/methods*
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Hematopoietic Stem Cell Transplantation
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Male
;
Follow-Up Studies
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Female
;
Lentivirus/genetics*
;
Child
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Child, Preschool
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Hematopoietic Stem Cells/metabolism*
;
Cerebroside-Sulfatase/metabolism*
;
Adolescent

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