1.Mechanism of Xielitang Against Ulcerative Colitis in Mice Based on "Intestinal Flora-bile Acid" Axis
Xiaotian WANG ; Yaning BIAO ; Yixin ZHANG ; Jian CHEN ; Ya GAO ; Yufang ZHANG ; Muqing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):30-38
ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group, a model group, a sulfasalazine group (0.6 g·kg-1), and low-, medium-, and high-dose Xielitang groups (1.67, 3.34, 6.68 g·kg-1). After treatment for 42 d, the colon length was recorded, and the disease activity index (DAI) score was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). Hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), liver receptor homolog-1 (LRH-1), cholesterol 7α-hydroxylase (CYP7A1), and fibroblast growth factor receptor 4 (FGFR4) in liver and FXR, sodium-dependent bile acid transporter (ASBT), and fibroblast growth factor 15 (FGF15) in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover, ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group, the model group showed significantly decreased colon length, IL-10 content, α-diversity index, abundance of Firmicutes and Lactobacillus, and content of deoxycholic acid (DCA) and lithocholic acid (LCA) (P<0.01), significantly increased DAI score, IL-6 and TNF-α content, abundance of Bacteroidetes, and the content of cholic acid (CA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA) (P<0.05, P<0.01), significantly down-regulated protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver (P<0.01). In addition, the structure of colonic mucosa was destroyed, and inflammatory cells infiltrated in the model group. Compared with the model group, Xielitang could significantly increase the colon length, IL-10 content, α-diversity index, the abundance of Firmicutes and Lactobacillus, and DCA and LCA content (P<0.05, P<0.01), decrease DAI score, abundance of Bacteroidetes, and the content of IL-6, TNF-α, CA, CDCA, and TCA (P<0.01), up-regulate the protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and down-regulate the protein expression of LRH-1 and CYP7A1 in liver (P<0.01). The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis, regulating intestinal flora imbalance, and maintaining bile acid homeostasis.
2.The predictive value of residual lipoprotein cholesterol combined with three-dimensional spot tracking technology for myocardial ischemia in patients with coronary heart disease
Hui WANG ; Yaning WANG ; Jianqing ZHE ; Yuan GAO ; Jin WANG
Journal of Chinese Physician 2025;27(5):673-677
Objective:To analyze the predictive value of residual lipoprotein cholesterol (RLP-C) combined with three-dimensional spot tracking (3D-STE) technology for myocardial ischemia in patients with coronary heart disease (CHD).Methods:A total of 158 patients with suspected CHD myocardial ischemia admitted to the First Affiliated Hospital of Xi′an Jiaotong University from March 2021 to August 2023 were selected and divided into the observation group (patients with myocardial ischemia) and the control group (patients with non-myocardial ischemia) according to the results of coronary angiography (CAG). The levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) of the patients were detected by the fully automatic biochemical analyzer, and the level of RLP-C was calculated. The 3D-STE technique was adopted to analyze the global long axis strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of the left ventricle of the patients. The differences of each index between the two groups were compared, the related influencing factors of myocardial ischemia in patients with CHD were analyzed, and the predictive value of RLP-C combined with 3D-STE technology for myocardial ischemia in patients with CHD was evaluated.Results:CAG revealed 39 patients (24.68%) with myocardial ischemia, with a total of 52 myocardial perfusion abnormalities, including 22 right coronary artery supply areas, 12 left coronary artery circumflex supply areas, and 18 anterior descending branch areas. The levels of cardiac function classification, GCS, GRS, GLS and RLP-C in the observation group were all better than those in the control group (all P<0.05). Binary logistic regression analysis showed that cardiac function classification grade Ⅳ, GCS, GRS, GLS, and RLP-C were the influencing factors of myocardial ischemia in patients with CHD (all P<0.05). Analysis of the receiver operating characteristic curve results showed that the sensitivities of cardiac function classification grade Ⅳ, GCS, GRS, RLP-C, GLS and the combination of the five in predicting myocardial ischemia in patients with CHD were 69.23%, 71.79%, 74.36%, 76.92%, 74.36% and 89.74%, respectively. The specificities were 68.91%, 71.43%, 75.63%, 77.31%, 76.47% and 88.24% respectively. The combined diagnosis of myocardial ischemia in patients with CHD with cardiac function classification grade Ⅳ, GCS, GRS, RLP-C and GLS had a relatively high value (all P<0.05). Conclusions:Cardiac function classification grade Ⅳ, GLS, GCS, GRS, and RLP-C are influencing factors of myocardial ischemia in patients with CHD. Combined detection is helpful to improve the diagnostic accuracy of myocardial ischemia.
3.The predictive value of residual lipoprotein cholesterol combined with three-dimensional spot tracking technology for myocardial ischemia in patients with coronary heart disease
Hui WANG ; Yaning WANG ; Jianqing ZHE ; Yuan GAO ; Jin WANG
Journal of Chinese Physician 2025;27(5):673-677
Objective:To analyze the predictive value of residual lipoprotein cholesterol (RLP-C) combined with three-dimensional spot tracking (3D-STE) technology for myocardial ischemia in patients with coronary heart disease (CHD).Methods:A total of 158 patients with suspected CHD myocardial ischemia admitted to the First Affiliated Hospital of Xi′an Jiaotong University from March 2021 to August 2023 were selected and divided into the observation group (patients with myocardial ischemia) and the control group (patients with non-myocardial ischemia) according to the results of coronary angiography (CAG). The levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) of the patients were detected by the fully automatic biochemical analyzer, and the level of RLP-C was calculated. The 3D-STE technique was adopted to analyze the global long axis strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of the left ventricle of the patients. The differences of each index between the two groups were compared, the related influencing factors of myocardial ischemia in patients with CHD were analyzed, and the predictive value of RLP-C combined with 3D-STE technology for myocardial ischemia in patients with CHD was evaluated.Results:CAG revealed 39 patients (24.68%) with myocardial ischemia, with a total of 52 myocardial perfusion abnormalities, including 22 right coronary artery supply areas, 12 left coronary artery circumflex supply areas, and 18 anterior descending branch areas. The levels of cardiac function classification, GCS, GRS, GLS and RLP-C in the observation group were all better than those in the control group (all P<0.05). Binary logistic regression analysis showed that cardiac function classification grade Ⅳ, GCS, GRS, GLS, and RLP-C were the influencing factors of myocardial ischemia in patients with CHD (all P<0.05). Analysis of the receiver operating characteristic curve results showed that the sensitivities of cardiac function classification grade Ⅳ, GCS, GRS, RLP-C, GLS and the combination of the five in predicting myocardial ischemia in patients with CHD were 69.23%, 71.79%, 74.36%, 76.92%, 74.36% and 89.74%, respectively. The specificities were 68.91%, 71.43%, 75.63%, 77.31%, 76.47% and 88.24% respectively. The combined diagnosis of myocardial ischemia in patients with CHD with cardiac function classification grade Ⅳ, GCS, GRS, RLP-C and GLS had a relatively high value (all P<0.05). Conclusions:Cardiac function classification grade Ⅳ, GLS, GCS, GRS, and RLP-C are influencing factors of myocardial ischemia in patients with CHD. Combined detection is helpful to improve the diagnostic accuracy of myocardial ischemia.
4.Relationship between perceived social support and family function in parents of pediatric liver transplant recipients: a chain mediation effect analysis
Yaning ZHU ; Yanhui LIU ; Ying JIANG ; Jing LI ; Wei GAO ; Zihang FENG ; Ying SUN ; Yiwei LUO ; Ruzhen LUO
Chinese Journal of Modern Nursing 2024;30(23):3110-3116
Objective:To investigate the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function in parents of pediatric liver transplant recipients.Methods:Totally 320 parents of pediatric liver transplant recipients who were treated at the Department of Pediatric Organ Transplantation, Tianjin First Central Hospital from April to October 2023 were selected by convenience sampling. The participants were surveyed using a general information questionnaire, the Perceived Social Support Scale (PSSS), the Acceptance and Action Questionnaire-Ⅱ (AAQ-Ⅱ), the Dyadic Coping Inventory (DCI), and the Family APGAR Index (APGAR). Pearson correlation analysis was used to examine the relationships between perceived social support, psychological flexibility, dyadic coping, and family function in these parents. Structural equation modeling (SEM) was performed using Amos 26.0 to analyze the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function, with the Bootstrap method used for model testing.Results:A total of 320 questionnaires were distributed, with 312 valid responses, yielding a response rate of 97.50% (312/320). The scores for the 312 parents were as follows: PSSS (59.29±15.64), AAQ-Ⅱ (20.35±9.07), DCI (124.64±32.65), and APGAR (6.98±2.74). Family function was positively correlated with perceived social support and dyadic coping ( P<0.01), and perceived social support was positively correlated with dyadic coping ( P<0.01). Psychological flexibility was negatively correlated with family function, perceived social support, and dyadic coping ( P<0.01). SEM results showed that psychological flexibility and dyadic coping had a significant chain mediation effect between perceived social support and family function, with a mediation effect value of 0.059. The chain mediation effect of psychological flexibility and dyadic coping accounted for 13.81% of the total effect (0.059/0.427) . Conclusions:Perceived social support directly affects family function in parents of pediatric liver transplant recipients and also indirectly influences family function through the chain mediation effect of psychological flexibility and dyadic coping.
5.Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis
Xiaotian WANG ; Yue WANG ; Yaning BIAO ; Jingmiao GAO ; Li LI ; Yangzi LU-AI ; Yunjie YIN ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):142-149
ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis (UC) mice induced by dextran sodium sulfate (DSS) and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group, model group, sulfasalazine group and and low-, medium-, and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group, other groups were given 1.5% DSS for 3 cycles of drinking (days 1-7, days 22-28 and days 43-49) and distilled water for the rest of the time (days 8-21, days 29-42 and days 50-63). After the first cycle, corresponding drugs were given for 42 days. The changes of general condition, body weight and disease activity index (DAI) score of mice were daily recorded during the experiment. At the end of the treatment, serum and colon tissue samples were collected, colon length was measured, intestinal weight index and colonic mucosal injury (CMDI) score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin (HE) staining. The levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The gene and protein expressions of Toll like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in colon tissue was detected by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultCompared with the normal group, the body weight, colon length and IL-10 content in the model group were significantly decreased (P<0.01), DAI score, intestinal weight index, CMDI score, IL-6 and TNF-α contents, and mRNA and protein expression levels of TLR4, NF-κB and HIF-1α in the model group were significantly increased (P<0.01). Moreover, the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group, body weight, colon length and IL-10 content in each dose group of Xielitang were significantly increased (P<0.05, P<0.01), DAI score, intestinal weight index and CMDI score, IL-6 and TNF-α contents, mRNA and protein expression levels of TLR4, NF-κB and HIF-1α were notably decreased (P<0.05, P<0.01). The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS, and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.
6.Broussonetiae Fructus Protects Against APAP-induced Liver Injury in Mice by Inhibiting Endoplasmic Reticulum Stress Pathway
Jingmiao GAO ; Tingting WANG ; Yaning BIAO ; Yaru GU ; Muqing ZHANG ; Xi WANG ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):66-73
ObjectiveTo explore the mechanism of Broussonetiae Fructus (BF) in preventing and treating drug-induced liver injury (DILI) induced by acetaminophen (APAP) through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group, model group, silybin group (3.4 g·kg-1), and high-, medium- and low-dose BF groups (3.0, 1.5, 0.75 g·kg-1), with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg-1, and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) were measured. Hematoxylin-eosin(HE) staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (T-AOC), glutathione (GSH), glutathione disulfide (GSSG), glutathione peroxidase (GSH-Px), and adenosine triphosphate (ATP) in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species (ROS) in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and c-Jun N-terminal kinase (JNK) in liver tissues was detected by Real-time quantitative polymerase chain reaction (PCR). ResultCompared with the normal group, the model group showed increased serum activities or content of ALT, AST, TBIL, and DBIL (P<0.01), increased MDA and GSSG contents (P<0.01), decreased contents or activities of SOD, T-AOC, GSH, GSH-Px, and ATP (P<0.01), swollen hepatocytes with inflammatory infiltration and lamellar necrosis, swollen and broken mitochondria of hepatocytes, and increased mRNA expression of GRP78, CHOP, and JNK (P<0.01). Compared with the model group, the groups with drug intervention showed decreased serum content or activities of ALT, AST, TBIL, and DBIL (P<0.05, P<0.01), reduced MDA and GSSG contents(P<0.05, P<0.01), and increased contents or activities of SOD, T-AOC, GSH, GSH-Px, and ATP (P<0.05, P<0.01), improved swollen hepatocytes, inflammatory infiltration, and lamellar necrosis, recovered bilayer membrane structure in mitochondria of hepatocytes, and decreased mRNA expression of GRP78, CHOP, and JNK (P<0.05, P<0.01). ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice, and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.
7.MouseVenue3D: A Markerless Three-Dimension Behavioral Tracking System for Matching Two-Photon Brain Imaging in Free-Moving Mice.
Yaning HAN ; Kang HUANG ; Ke CHEN ; Hongli PAN ; Furong JU ; Yueyue LONG ; Gao GAO ; Runlong WU ; Aimin WANG ; Liping WANG ; Pengfei WEI
Neuroscience Bulletin 2022;38(3):303-317
Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional (3-D) space. However, there is no available three-dimensional behavior capture system that focuses on rodents. Here, we present MouseVenue3D, an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents. We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module. Then, we validated this process in behavior recognition tasks, and showed that 3-D behavioral data achieved higher accuracy than 2-D data. Subsequently, MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse. Finally, we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice. Our findings reveal that subtle, spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.
Animals
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Behavior, Animal
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Brain/diagnostic imaging*
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Imaging, Three-Dimensional/methods*
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Mice
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Neuroimaging
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Rodentia
8.Recent advances in developing small-molecule inhibitors against SARS-CoV-2.
Rong XIANG ; Zhengsen YU ; Yang WANG ; Lili WANG ; Shanshan HUO ; Yanbai LI ; Ruiying LIANG ; Qinghong HAO ; Tianlei YING ; Yaning GAO ; Fei YU ; Shibo JIANG
Acta Pharmaceutica Sinica B 2022;12(4):1591-1623
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
10.Clinical study on transcription and protein expression of tumor necrosis factor α mRNA in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure
Xiaoli GAO ; Yinghua LIU ; Xiaokun ZHANG ; Shenqing CUI ; Ming XIE ; Yaning LIU ; Jianbing WANG ; Aifeng GU ; Chengjuan YU
The Journal of Practical Medicine 2019;35(3):412-415
Objective The study was to investigate the activation of tumor necrosis factor α (TNF-α) mRNA transcription and protein expression in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure. Methods From February 2015 to April 2018, 244 patients with heart failure in the cardiovascular department of our hospital were selected as heart failure group, while 244 healthy cases were enrolled as the control group at the same time. The peripheral blood samples of two groups were collected. We detected the transcription and protein expression of TNF-α mRNA and the activation of PI3K, AKT in peripheral blood. The left ventricular ejection fraction (LVEF) were measured in two groups. The correlations between influencing factors and LVEF were analyzed. Results The levels of PI3K, AKT in the heart failure group were higher than those in the control group. The differences were statistically significant respectively (P < 0.05). The mRNA relative content and protein content of TNF-α in peripheral blood mononuclear cells of heart failure group were higher compared with those of control group (P < 0.05). The LVEF of heart failure group was significantly lower than that of the control group (34.50 ± 6.33) % versus (55.60 ± 2.49) %, P < 0.001). Among 244 patients with heart failure, Spearman correlation analysis showed that there were significant positive correlations between TNF-a mRNA and protein expression levels and the levels of PI3K, AKT respectively (P < 0.05). Multiple factors unconditional Logistic regression analysis showed that the TNF-α mRNA, protein expression and PI3K, AKT levels in peripheral blood were independent risk factors for LVEF (P < 0.05). Conclusion The expression levels of PI3K, AKT and TNF-α are all significantly increased in chronic heart failure patients, which could participate in the occurrence and development of heart failure.

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