1.Regulatory effect of Jiedu Huayu granules on liver injury in mice with acute liver failure and its mechanism
Chengyu YA ; Tingshuai WANG ; Huiping YAN ; Yi WANG ; Qingrui ZHAO ; Shenglan ZENG ; Weiyu CHEN ; Rongzhen ZHANG
Journal of Clinical Hepatology 2026;42(1):143-150
ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure (ALF) by observing its effect on a mouse model of ALF after prophylactic administration, and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group, model group, Jiedu Huayu granules group (JDHY group), and farnesoid X receptor (FXR) agonist (GW4064) group using a random number table, with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling, those in the normal group and the model group were given 0.9% NaCl solution by gavage, and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling, and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin (TBil), total bile acids (TBA), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in mice from each group; HE staining was used to observe liver pathological changes; RT-PCR was used to measure the mRNA expression levels of FXR, fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), small heterodimer partner (SHP), and bile salt export pump (BSEP) in mice, and Western blot was used to measure the protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP. A one-way analysis of variance was used for comparison between groups, and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group, the model group had significant increases in the serum levels of TBil, ALT, AST, TBA, and GGT (all P<0.01), and compared with the model group, the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil, ALT, AST, TBA, and GGT (all P <0.01). HE staining showed that compared with the model group, the JDHY group and the GW4064 group had milder pathological injury, a reduction in the area of hepatocyte necrosis, and alleviation of cellular swelling and edema. Compared with the normal group, the model group had significant reductions in the mRNA and protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP in liver tissue (all P <0.01), and compared with the model group, the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP in liver tissue (all P <0.05). ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.
2.Mechanism of Huangqi Guizhi Wuwu decoction in ameliorating cerebral ischemia injury via the Nrf2/HO-1 pathway
Chengyu QIAN ; Linsheng WANG ; Jing ZHANG ; Tao WANG ; Weidong QIAN
Journal of China Pharmaceutical University 2026;57(1):98-107
This study aimed to investigate the protective effects of Huangqi Guizhi Wuwu decoction (HGWD) against cerebral ischemic injury and the underlying mechanisms. A middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice to evaluate the effects of HGWD on neurobehavioral scores, cerebral infarction rate, brain water content, and oxidative stress and inflammatory markers. The mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in brain tissue were assessed. In addition, Nrf2 knockout mice were used to verify the role of Nrf2 in the protective effects of HGWD against MCAO-induced injury. Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary neuronal cells was employed to further confirm the pharmacological effects of HGWD in vitro. The results showed that HGWD significantly ameliorated cerebral ischemic injury in MCAO mice, alleviated oxidative stress, suppressed the release of inflammatory factors, and markedly upregulated the expression of Nrf2, HO-1, and Bcl-2 while downregulating Bax expression, with consistent trends being observed at both mRNA and protein levels. The protective effects of HGWD were significantly attenuated in Nrf2 knockout mice, indicating the pivotal role of Nrf2 in HGWD-mediated protection against cerebral ischemic injury. In vitro experiments revealed that HGWD significantly increased neuronal cell viability, reduced lactate dehydrogenase(LDH) leakage, and decreased apoptosis in OGD/R-treated cells, accompanied by upregulation of Nrf2, HO-1, and Bcl-2 and downregulation of Bax. In conclusion, HGWD protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and modulating the Bcl-2/Bax signaling pathway to inhibit apoptosis, thereby protecting brain cells from ischemic damage.
3.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
4.Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice
Changrui LONG ; Shijian XIANG ; Zhenhua ZHANG ; Huixing WU ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2025;36(6):668-673
OBJECTIVE To investigate the improvement mechanism of hyperoside (HYP) on non-alcoholic fatty liver disease (NAFLD). METHODS Male C57BL/6 mice were randomly divided into normal (NFD) group, model (HFD) group and HYP group, with 8 mice in each group. Except for NFD group, the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model; HYP group was simultaneously given HYP 100 mg/kg intragastrically every day, for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication; the histopathological changes and lipid accumulation in the liver were observed, and the contents of triglyceride (TAG) in liver tissue and serum contents of TAG, aspartate transaminase (AST) and alanine transaminase (ALT) were measured; LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis, and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α (PPARα) were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group, model group, HYP low-concentration group (50 μmol/L), HYP high-concentration group (100 μmol/L), HYP low-concentration+GW6471 (PPARαinhibitor) group, and HYP high-concentration+GW6471 group. Except for normal control group, the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed, and the TAG content was detected. RESULTS Compared with HFD group, HYP group exhibited significant reductions in liver fat vacuoles, lipid accumulation, liver weight, and TAG content in liver tissue, as well as serum contents of ALT, AST and TAG (P<0.05). Additionally, the expression of PPARα protein in liver tissue was significantly increased (P<0.05), and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG, diacylglycerol and other lipids in the liver. Compared with model group, cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups (P<0.05); GW6471 could significantly reverse the improvement effect of HYP on above indicators (P<0.05). CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice, and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.
5.The reduction of reproductive function of male zebrafish caused by high-fat diet:A molecular basis study
Zhenghong DU ; Fei MAO ; Xue ZHAO ; Shuo WANG ; Yongjun WAN ; Chengyu ZHANG ; Peng DUAN ; Dahu ZHANG
National Journal of Andrology 2025;31(11):963-971
Objective To investigate the effects and mechanisms of high-fat diet(HFD)-induced obesity on male ze-brafish reproductive function.Methods Adult male zebrafish were divided into normal diet(ND)group and HFD group.Growth and metabolic conditions were evaluated by measuring body weight,body length,BMI,organ index,and glucose/lipid lev-els.Reproductive capacity was assessed via sperm concentration,motility,fertilization rate,and testosterone levels.Testicular tissues from both of groups were subjected to transeriptomic sequencing(RNA-seq).And qRT-PCR was used to validate the expression of genes.Results Compared to male zebrafish in ND group,the ones in HFD group exhibited hepatic steatosis and glucose/lipid meta-bolic disorders(P<0.05).Testicular structural disorganization,along with reduced testosterone levels,decreased gonadosomatic in-dex,and impaired sperm concentration and motility occurred in HFD group(P<0.05).GO analysis revealed that differentially ex-pressed genes were enriched in spermatogenesis and ciliary system,while KEGG analysis highlighted metabolic related pathways(pu-rine metabolism,thyroid hormone synthesis,mTOR signaling)and cell adhesion molecules.Twenty key differentially expressed genes were validated by qRT-PCR,which confirmed the reliability of RNA-Seq results.Conclusion Impairment of reproductive function induced by HFD in zebrafish may be associated with three regulatory mechanisms including ciliary system,metabolic dysregulation,and aberrant cell adhesion molecule signaling.This study provides mechanistic insights and identifies potential therapeutic targets for clinical management of diet-associated infertility.
6.Efficacy of inverted triangular cannulated screw internal fixation for femoral neck fracture in young and middle-aged patients
Fei MENG ; Min LIU ; Minggang YUAN ; Linjiang CUI ; Chengyu LYU ; Haining ZHANG ; Lixin LI
Chinese Journal of Trauma 2025;41(1):58-64
Objective:To compare the efficacy of inverted triangular and equilateral triangular cannulated screw internal fixation (CSIF) in the treatment of femoral neck fracture (FNF) in young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 52 patients with FNF admitted to Qingdao Central Hospital of Rehabilitation University from January 2020 to January 2022, including 18 males and 34 females, aged 28-60 years [(45.7±9.3)years]. Based on the Garden classification, the fractures were classified as type I in 11 patients, type II in 34, and type III in 7. According to Pauwels classification, the fractures were classified as type I in 33 patients, type II in 13, and type III in 6. Among them, 28 patients received inverted triangular CSIF (inverted triangle group) and 24 received equilateral triangular CSIF (equilateral triangle group). Before surgery and at 3 months after surgery, nuclear medicine three-phase bone scan and bone tomography imaging were performed to evaluate the proximal blood supply recovery in the fractured sites in the two groups. The Harris hip joint function scores before surgery, at 1 day, 3 months after surgery, and at the last follow-up, the posterior tilt angles of the femoral head before surgery and at 3 months after surgery, and the fracture nonunion rate and ischemic necrosis rate of the femoral head at the last follow-up were compared between the two groups.Results:All the patients were followed up for 18-30 months [(24.2±5.6)months]. Before surgery, the fracture of both groups showed extensive blood supply defects at the proximal end. At 3 months after surgery, the excellent and good rate of the proximal blood supply recovery in the inverted triangle group was 92.9% (26/28), significantly higher than 70.8% (17/24) in the equilateral triangle group ( P<0.05). The Harris hip joint function scores before surgery were (44.1±4.1)points and (43.5±5.1)points in the inverted triangle group and equilateral triangle group ( P>0.05). At 1 day, 3 months after surgery, and at the last follow-up, the Harris hip joint function scores in the inverted triangle group were (71.7±3.6)points, (87.0±3.6)points, and (88.7±2.6)points respectively, higher than those in the equilateral triangle group [(65.0±5.4)points, (80.5±5.2)points, and (82.6±4.0)points] ( P<0.05). In both groups, there were no significant differences between the Harris hip joint function scores at the last follow-up and those at 3 months after surgery ( P>0.05), which were all higher than those at 1 day after surgery ( P<0.05). The posterior tilt angles of the femoral head were (16.9±4.4)° and (16.8±5.0)° in the inverted triangle group and equilateral triangle group preoperatively ( P>0.05). At 3 months after surgery, the posterior tilt angles of the inverted femoral head were (8.9±1.9)° and (9.0±1.8)° in the inverted triangle group and equilateral triangle group ( P>0.05). The posterior tilt angles of the femoral head at 3 months after surgery were lower than those before surgery in both groups ( P<0.05). At the last follow-up, there were no statistically significant differences in the fracture nonunion rate and ischemic necrosis rate of the femoral head between the two groups ( P>0.05). Conclusion:Compared with equilateral triangle CSIF, inverted triangle CSIF achieves better recovery of the proximal blood supply and hip joint function in the treatment of femoral neck fracture in young and middle-aged patients.
7.Study of Jiedu Huayu granules on antagonizing intestinal endotoxemia in liver failure by improving inflammation and intestinal barrier damage
Tingshuai WANG ; Riyun ZHANG ; Chengyu YA ; Dewen MAO ; Rongzhen ZHANG
Chinese Journal of Hepatology 2025;33(9):872-879
Objective:To study the mechanistic role of Jiedu Huayu granule in improving intestinal mucosal barrier functional damage and protecting against liver failure in mice induced by D-galactosamine combined with lipopolysaccharide.Methods:Fifty mice were randomly divided into a normal group, a model group, a low-dose Jiedu Huayu granule group (4.16 g·kg -1·d -1), a medium-dose Jiedu Huayu granule group (8.32 g·kg -1·d -1), and a high-dose Jiedu Huayu granule group (16.64 g·kg -1·d -1). D-galactosamine combined with lipopolysaccharide was administered once to establish an acute liver failure mouse model, followed by corresponding drug intervention. Retro-orbital blood samples were collected to measure serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels six hours after modeling in mice. The endotoxin content was detected using the limulus reagent method. The content of serum interleukin-1β, tumor necrosis factor-α, and interferon-γ levels were detected using enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe liver and intestinal pathological tissues.Western blot and RT-PCR were used to determine the protein and mRNA expression of Occludin, Zo-1, Tricellulin, and CLDN3 in intestinal tissues. Multiple quantitative data were analyzed using one-way ANOVA, following a normal distribution. LSD-t test was used for statistical analysis between inter-groups. Results:The medium-and high-dose Jiedu Huayu granules had reduced and improved liver function impairment, liver pathological tissue damage, intestinal barrier damage, serum endotoxin and inflammatory factors ( P<0.05), and increased intestinal expression of occludin, Zo-1, Tricellulin, and CLDN3 ( P<0.05) in mice group with acute liver failure. Conclusion:Jiedu Huayu granules can reduce liver inflammatory damage, gut-derived endotoxemia, bacterial endotoxins entering the liver, and protect intestinal barrier function, thereby remissioning liver inflammation and antagonizing liver failure in mice with acute liver failure.
8.HJT-sRNA-m7 bencaosome modulates fibrosis progression in a silicosis mouse model
Jiahui CHANG ; Pengju REN ; Yunyi ZHOU ; Chengyu JIANG ; Yanli ZHANG
Basic & Clinical Medicine 2025;45(7):874-881
Objective To explore the role and mechanism of HJT-sRNA-m7(M7)bencaosome in a silicosis mouse model.Methods C57BL/6J mice were randomly divided into four groups:blank,control,negative control(NC)oligonucleotide,and M7 treatment(HJT-sRNA-m7 bencaosome)groups.After three rounds of pretreatment with HJT-sRNA-m7 bencaosome,all groups except the blank one were modeled via a single intratracheal exposure.Each mouse received 50 μL of a silica suspension at a dose of 200 mg/kg body weight via intratracheal instillation.From day 6 to day 26,the bencaosome was administered every other day via oral gavages.On day 28,pulmonary function tests were performed.Bronchoalveolar lavage fluid was collected for flow cytometry and cytokine analysis.The left lung was harvested for histopathological examination and Masson's trichrome staining to evaluate collagen fiber dep-osition.The right lung was used for hydroxyproline quantification to assess collagen accumulation.Results The re-sults of pulmonary function test,pathological analysis and hydroxyproline measurements all indicated that M7 ben-caosome treatment significantly alleviated silica-induced pulmonary fibrosis.Moreover,flow cytometry analysis of BALF confirmed that M7 bencaosome inhibited the silica-induced inflammatory response,that was supported by cy-tokine analysis.Conclusions HJT-sRNA-m7 bencaosome is quite effective to treat silicosis and inhibits mitigating pulmonary fibrosis progression in mouse models.
9.Network pharmacology-based screening and validation of tea-derived small molecules against lung cancer
Rui YANG ; Sifen DU ; Lehui JIANG ; Tian FU ; Pengju REN ; Chengyu JIANG ; Yanli ZHANG
Basic & Clinical Medicine 2025;45(7):939-946
Objective To screen the active chemical components with potential therapeutic effects against lung cancer in tea and to provide new insights into the treatment and prevention of lung cancer.Methods Based on net-work pharmacology,the main active components from 13 types of tea samples were analyzed using liquid chromatog-raphy-mass spectrometry(LC-MS).The targets of these small molecules were obtained from the BATMAN-TCM da-tabase to construct a"component-target-disease"network.Lung cancer-related disease targets were retrieved from the GeneCard and Malacard databases followed by Gene Ontology(GO)functional and KEGG pathway enrichment analyses of potential pharmacological targets.A protein-protein interaction(PPI)network was constructed using the STRING database.The molecular docking was employed to screen small molecules with potential anti-cancer ac-tivity,and their potential inhibition to proliferation of human non-small cell lung cancer cell line A549 and human large cell lung cancer cell line H460.Results A total of 37 active components and 429 targets were identified in tea,with 182 overlapping targets associated with lung cancer.GO analysis revealed that these targets were primarily involved in biological processes such as cell proliferation,response to stimuli,and metabolic processes.KEGG pathway analysis indicated that these targets were mainly enriched in the p53 signaling pathway,ErbB signaling pathway,and PI3K-Akt signaling pathway.PPI network analysis identified key targets including MAPK1,AKT1,SRC,MAPK3,and p53.Molecular docking screened coumestrol as a molecule capable of binding to human estro-gen receptor 2(ESR2),and its inhibitory effect on the proliferation of A549 and H460 cells was experimentally validated(P<0.000 1).Conclusions The active components in tea may intervene in the development and progres-sion of lung cancer through a multi-component,multi-target,and multi-pathway mechanism,The results suggests po-tential components against lung cancer in tea,which may be applied in the prevention of human lung cancer.
10.Arteriosclerosis detection method based on oscillometric upper-arm cuff pressure wave
Ziqi ZHANG ; Yumin LI ; Jianqing LI ; Chengyu LIU
Chinese Journal of Medical Physics 2025;42(8):1079-1085
Objective To present an assessment method based on oscillometric upper-arm cuff pressure wave for realizing home-based detection of arteriosclerosis.Methods An upper-arm cuff pressure wave acquisition device based on an electronic blood pressure monitor was designed to implement data collection for cuff inflation and deflation,as well as the 15 s pressure holding phase.Following preprocessing of the data collected during this holding phase,individual pulse waves were extracted for pulse decomposition analysis(PDA).A novel model that superimposed a logarithmic normal function with two Gaussian functions,and an optimization method that combined template matching and particle swarm optimization were proposed to efficiently and accurately extract PDA features.Gaussian process regression was employed for multifeature fusion analysis,leading to the proposal of a new predictive indicator for arteriosclerosis.Results The mean absolute error of PDA was less than 1.2%,and the average processing time for a single pulse wave was less than 0.2 s.The regression determination coefficient R2 between the obtained indicators and baPWV was 0.8178.Conclusion The analysis on upper-arm cuff pressure wave provides a new reference for non-invasive arteriosclerosis detection,and it can be applied to electronic blood pressure monitors for home-based monitoring,offering significant practical value.


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