1.Mechanisms of Improving Hippocampal Synaptic Plasticity Through GLP-1/GLP-1r Pathway to Alleviate Anxiety and Depression-like Behaviors in Chronic Restraint Stress Rats by Xiaoyaosan
Hao WANG ; Yanan YAN ; Jiepeng WANG ; Chaoyi FANG ; Fang FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):34-42
ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1r) and protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress (CRS),and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley (SD) rats were randomly divided into normal,model,Xiaoyaosan,and fluoxetine groups,with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules (7.36 g·kg-1·d-1),while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine (2 mg·kg-1·d-1). Body weight was measured on days 0,7,14,and 21 of the experiment. On days 0 and 22 of the experiment,the sucrose preference test (SPT),forced swimming test (FST),and open field test (OFT) were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 (PSD95) and synapsin (SYP) was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling,compared with the normal group,the rats of the model group had anxiety and depression-like behavioral manifestations,neuronal damage in the hippocampal CA1 region,significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes (P<0.01),and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). Compared with the model group,the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors,reduced neuronal damage in the hippocampal CA1 region, significantly increased expression of PSD95 and SYP genes (P<0.01),and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.
2.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P0.01), whereas it was significantly increased in the Sini San group compared with the model group (P0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P0.05), and compared with the model group, both were significantly increased in the Sini San group (P0.05, P0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P0.05, P0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
3.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P<0.01), whereas it was significantly increased in the Sini San group compared with the model group (P<0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P<0.05), and compared with the model group, both were significantly increased in the Sini San group (P<0.05, P<0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P<0.05, P<0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P<0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
4.Pharmacodynamic Substances and Mechanisms of Xinglou Chengqi Tang in Treating Post-stroke Complications: A Review
Yujin ZHANG ; Xiangzhuo LIU ; Zhouyang CHEN ; Zihao SONG ; Xinyi LIU ; Yizhi YAN ; Chaoya LI ; Yingyan FANG ; Shasha YANG ; Xueqin CHENG ; Zhou XIE ; Sijie TAN ; Peng ZENG ; Yue ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):327-337
Stroke is the leading cause of death and disability among adults in China, and its common complications include digestive system abnormalities, cognitive impairment, depression, stroke-associated pneumonia, and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang (XLCQT) is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically, XLCQT is often used to treat stroke and its complications. However, the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally, since the basic research is weak, the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis, medicinal properties, safety evaluation, and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients, resveratrol, kaempferol, luteolin, chrysoeriol, apigenin, (+)-catechin, and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex, including inflammatory response, brain-gut axis, hypothalamic-pituitary-adrenal (HPA) axis, intestinal flora, neurotrophic factors, autophagy, oxidative stress, and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.
5.Correlation of Symptom Burden and Nutritional Status of Patients with Cancer in Chemotherapy Stage Under Guidance of TCM Constitution
Bailu SUI ; Yuhang FANG ; Yi XIE ; Yan WANG ; Ying ZHANG
Cancer Research on Prevention and Treatment 2026;53(2):127-132
Objective To investigate the relationship between symptom burden and nutritional status under Traditional Chinese Medicine (TCM) constitution classification in patients undergoing chemotherapy. Methods Data on the physical constitution, symptom burden, and nutritional status of 640 patients with malignant tumors within the 21st–28th days of chemotherapy treatment were collected and analyzed. Results Symptom burden was found to have a positive correlation with nutritional risk and TCM bias (except for idiosyncrasies), suggesting that constitution bias may be an important internal factor for the aggravation of clinical symptoms and malnutrition in patients with cancer. Conclusion The relationship between symptom burden and nutritional status in chemotherapy under the guidance of TCM constitution can be studied to predict the nutritional status and symptom burden of patients after chemotherapy to guide the symptom and nutritional management of patients with cancer in the chemotherapy stage.
6.Gualou Xiebai Banxiatang in Treatment of Cardiovascular Diseases: A Review
Yalong KANG ; Bo NING ; Juanjuan TAN ; Hongfei QI ; Yan SHI ; Fang GUAN ; Haifang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):256-267
Cardiovascular diseases (CVD),a group of common diseases in clinical practice,are witnessing a steady rise in both incidence and mortality rates,posing a challenge to public health. Gualou Xiebai Banxiatang,originating from Synopsis of the Golden Chamber (《金匮要略》),was initially used to treat severe cases of chest impediment. The formula consists of Trichosanthis Fructus,Allii Macrostemonis Bulbus,Pinelliae Rhizoma,and Baijiu. It has a wide range of clinical applications,with therapeutic effects including moving Qi to relieve depression,activating Yang to dissipate mass,and expelling phlegm to alleviate chest congestion. In recent years,clinical research has confirmed that Gualou Xiebai Banxiatang,with or without modification,used alone or in combination with Western medicine,has definite effects in the treatment of CVD such as hyperlipidemia,coronary atherosclerotic heart disease,hypertension,heart failure,and arrhythmia. It can alleviate disease symptoms and reduce the risk of re-hospitalization. Basic research indicates that the mechanisms of Gualou Xiebai Banxiatang include improving endothelial functions,exhibiting anti-inflammatory properties,countering oxidative stress,preventing apoptosis,inhibiting ventricular remodeling,regulating mitochondrial functions,improving hemorheology,and modulating autophagy and neurotransmitters. This article reviews relevant articles in recent years with focuses on the compatibility,clinical application,and mechanism of Gualou Xiebai Banxiatang. This review is expected to provide a theoretical basis for the mechanism research and clinical application of this formula in treating CVD and to offer ideas and reference for in-depth research.
7.Effect of Stattic on the survival of mouse heart allograft by regulating memory CD4+T cell-mediated acute rejection
Shiliang LI ; Yi FENG ; Ming FANG ; Yan ZHOU
Organ Transplantation 2025;16(1):74-82
Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4+ T cells (CD4+Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm, and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4+Tm (CD4+CD44+CD62L+) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4+Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4+Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4+Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4+Tm- mediated acute rejection.
8.POEMS syndrome with hepatosplenomegaly as the initial manifestation: A report of two cases
Ye ZHANG ; Wenqing WANG ; Jing LI ; Qianrong BAI ; Jiayu LI ; Yan CHENG ; Miaomiao FANG ; Nana GAO ; Changxing HUANG
Journal of Clinical Hepatology 2025;41(1):127-132
POEMS syndrome is a rare condition associated with plasma cell disorders, and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease, the patients presented with lower limb weakness, hepatosplenomegaly, lymph node enlargement, ascites, hypothyroidism, positive M protein, and skin hyperpigmentation, and 18F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome, and the symptoms were relieved after immunomodulatory treatment.
9.Visualization Analysis of Research Hotspots and Trends in Field of Tumor Therapy Based on CiteSpace and VOSviewer
Yuhang FANG ; Chuchu ZHANG ; Bailu SUI ; Yan WANG ; Runxi WANG ; Yu CHEN ; Xinhe YUAN ; Hongjun YANG ; Ying ZHANG
Cancer Research on Prevention and Treatment 2025;52(4):297-304
Objective To explore the research hotspots and development trends in the field of cancer treatment in the past decade. Methods The CNKI and Web of Science Core Collection databases were searched for Chinese and English articles related to cancer treatment published over the last 10 years. Bibliometric research methods were employed, including keyword cluster analysis of published literature. Results A total of 45 455 Chinese articles and 866 958 English articles were retrieved. Combining the visualization analysis results and the current research dilemma of tumor treatment revealed that the current research hotspots of tumor treatment domestically and internationally can primarily focus on four key areas. In the realm of targeted therapy, efforts are directed towards the discovery of new drug targets, overcoming resistance to targeted therapy, and the development of monoclonal antibodies and antibody–drug conjugates. In the field of immunotherapy, the emphasis lies in enhancing the response rate to immune checkpoint inhibitors, determining the mechanisms behind resistance to immunotherapy, and improving the safety of treatment. The research in traditional Chinese medicine (TCM) covers evidence-based evaluation studies on TCM treatment, the identification of populations that can gain the most benefit from TCM, and strategies for improving the quality of life. In the area of novel drug development, cutting-edge technologies, such as organoid-based screening for anticancer drugs, synthetic biology, and artificial intelligence, are under investigation. Conclusion New targeted drugs, immune efficacy improvement, multidisciplinary integration, nano-delivery, and TCM innovation are the key research directions in the field of tumor therapy in the future.
10.Diagnosis and Treatment of Cough Associated with Interstitial Lung Disease from Collaterals Deficiency with Latent Wind
Fang SUN ; Shiqi SUN ; Yan XUE ; Wei ZHANG
Journal of Traditional Chinese Medicine 2025;66(10):1057-1059
It is believed that the basic mechanism of cough associated with interstitial lung disease is collaterals deficiency with latent wind: the deficiency of the lung organs and lung collaterals is the basis of its pathogenesis, and latent wind in lung collaterals is the key mechanism of the cough which is difficult to cure. Treatment is based on the principle of supplementing deficiency and treating wind, dispelling the pathogens and unblocking the collaterals. Supplementing deficiency should supplement lungs, boost kidneys, and strengthen spleens to consolidate the root and banking up the origin, and regulate and tonify the lung collaterals; dispelling the pathogens should treat the internal and external winds at the same time, and taking into account the combined pathogens of phlegm, stasis and dampness to clear the stagnation of the lung collaterals.

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