1.Effect of Quercetin on Cuproptosis in Rheumatoid Arthritis Rats and Its Mechanism via SLC31A1/FDX1 Pathway
Haoruo YANG ; Qiuai KOU ; Junhua REN ; Guo YUAN ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):121-130
ObjectiveTo observe the influence and therapeutic effect of quercetin on cuproptosis in rheumatoid arthritis rats and to explore its possible mechanism based on the solute carrier family 31 member 1 (SLC31A1)/ferredoxin 1 (FDX1) pathway. MethodsSixty male SD rats were divided into six groups: A control group, a model group, high- and low-dose quercetin groups (150 and 50 mg·kg-1), a cuproptosis inhibitor (tetrathiomolybdate, TTM) group (10 mg·kg-1), and a methotrexate group (2 mg·kg-1), 10 rats in each group. Except for the control group, the model of rheumatoid arthritis (CIA) rats was established by type Ⅱ collagen induction method. After successful modeling, each drug group was intervened according to the corresponding dose of drugs, and the control group and the model group were given the same amount of normal saline by gavage, once a day, which lasted for 4 weeks. The swelling degree of rats' feet was observed, and the clinical arthritis scores were determined. The levels of serum rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), and ceruloplasmin (Cp) were detected by enzyme-linked immunosorbent assay (ELISA). The content of copper ion (Cu), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in joint tissue was detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of joint tissue. The levels of reactive oxygen species (ROS) and dihydrolipoic acid transacetylase (DLAT) were detected by immunofluorescence (IF). The protein and mRNA expression of SLC31A1, FDX1, lipoic acid synthase (LIAS), heat shock protein 70 (HSP70), pyruvate dehydrogenase E1 subunit β (PDHB), and copper transporting P-type ATPase β (ATP7B) was detected by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared to the control group, the model group exhibited joint swelling and deformity, significantly increased clinical arthritis scores, obvious bone destruction, synovial hyperplasia, and inflammatory cell infiltration in joint tissue. In addition, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp showed significant elevation, while the level of IL-10 was significantly reduced. The levels of Cu, MDA, ROS, and DLAT in joint tissue were markedly increased, whereas SOD and GSH content was significantly decreased. The protein and mRNA expression of SLC31A1 and HSP70 was significantly up-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was significantly down-regulated (P<0.01). Compared to the model group, each treatment group exhibited varying degrees of improvement in joint swelling and deformation as well as clinical arthritis scores in rats. Additionally, there was a reduction in joint bone destruction, inflammatory cell infiltration, and synovial hyperplasia in rats. Furthermore, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp significantly decreased, while the level of IL-10 increased significantly. In joint tissue, the levels of Cu, MDA, ROS, and DLAT showed significant decreases, while SOD and GSH content exhibited significant increases. The protein and mRNA expression of SLC31A1 and HSP70 was down-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was up-regulated (P<0.05). ConclusionQuercetin effectively reduces synovial hyperplasia and inflammatory infiltration in rats with rheumatoid arthritis, thereby alleviating pathological damage to joint tissue. This effect may be attributed to the blockade of the SLC31A1/FDX1 signaling pathway activation and inhibition of excessive cuproptosis.
2.Establishment of a Gastrointestinal-Brain Inter-Organ Multimodal Characterization System Based on Traditional Chinese Medicine Theory and Its Application in Refractory Diseases
Guanghui HAN ; Yan GUO ; Peijing RONG ; Bin CONG ; Shuangjiang LIU ; Shaoyuan LI ; Wei WEI
Journal of Traditional Chinese Medicine 2025;66(6):561-568
The concept of holism is the core idea of traditional Chinese medicine (TCM). Various organs and tissues coordinate with each other to maintain the body's life activities, with a close and mutual influence between the spleen, stomach, and the central nervous system (brain). The gut-brain axis plays an important bridging role between the digestive system and the central nervous system, achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence, coordination, and integration between different organs and systems; multimodality, on the other hand, utilizes multiple sensory modalities, such as vision, hearing, and touch, to convey information. By combining TCM theory with the gut-brain axis theory, a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders, precancerous gastrointestinal diseases, Alzheimer's disease, Parkinson's syndrome, type 2 diabetes, and depression.
3.Research Progress on Animal Models for Hernia Diseases and New Hernia Repair Materials
Bin FEI ; Wenke GUO ; Jianping GUO
Laboratory Animal and Comparative Medicine 2025;45(1):55-66
Hernia is a common and frequently occurring condition in general surgery, referring to the displacement of an organ or part of an organ from its normal anatomical position through a congenital or acquired weak point, defect, or space into another area. Its pathogenesis is complex, involving multiple factors such as abdominal wall weakness or increased intra-abdominal pressure. The clinical manifestations of hernia vary depending on its type, location, and severity. As the aging of the population continues to advance, the incidence of hernia has been increasing annually. Animal models serve as an important tool in hernia research. They enable the evaluation of the safety and efficacy of new repair materials and techniques, as well as assisting clinicians in developing new surgical methods and investigating the mechanisms and novel therapies for certain hernia diseases and their complications. Given the significant differences in the pathophysiological mechanisms of different types of hernia diseases, the methods and evaluation criteria for establishing animal models are highly diverse. Furthermore, the methods for establishing animal models are closely related to experimental objectives, and different experimental goals require different animal models. Therefore, selecting appropriate animal models based on experimental objectives is crucial for ensuring the smooth progress of research and obtaining reliable results. To this end, this review summarizes effective methods for establishing animal models for external abdominal hernias (including incisional hernia, inguinal hernia, umbilical hernia, parastomal hernia, incarcerated hernia, and pelvic floor hernia), congenital diaphragmatic hernia, hiatal hernia, and cerebral hernia. It provides a detailed analysis of the advantages, disadvantages, and evaluation criteria of these models. Additionally, this review summarizes recent preclinical applications of new hernia repair materials, aiming to provide references for animal experimental research in the field of hernia studies.
4.Role of amino acid metabolism in autoimmune hepatitis and related therapeutic targets
Peipei GUO ; Yang XU ; Jiaqi SHI ; Yang WU ; Lixia LU ; Bin LI ; Xiaohui YU
Journal of Clinical Hepatology 2025;41(3):547-551
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear, but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system, while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH, in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.
5.Analysis of distortion product otoacoustic emissions results of noise-exposed workers at a metal shipbuilding enterprise
Jieting ZHOU ; Jianyu GUO ; Hairu YANG ; Linyan SHU ; Zhixing FAN ; Jia TANG ; Xinqiang NIE ; Guoyong XU ; Hansheng LIN ; Bin XIAO
China Occupational Medicine 2025;52(1):99-105
Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.
6.Dynamics of eosinophil infiltration and microglia activation in brain tissues of mice infected with Angiostrongylus cantonensis
Fanna WEI ; Renjie ZHANG ; Yahong HU ; Xiaoyu QIN ; Yunhai GUO ; Xiaojin MO ; Yan LU ; Jiahui SUN ; Yan ZHOU ; Jiatian GUO ; Peng SONG ; Yanhong CHU ; Bin XU ; Ting ZHANG ; Yuchun CAI ; Muxin CHEN
Chinese Journal of Schistosomiasis Control 2025;37(2):163-175
Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.
7.Preliminary development of Health Literacy Evaluation Scale for Chinese High School Students
GUO Shihao, ZHU Fan, ZHU Guiyin, QI Tiantian, YANG Shuang, HU Bin, WU Huiyun, JIANG He, MA Yinghua
Chinese Journal of School Health 2025;46(5):676-680
Objective:
To develop a health literacy evaluation scale for Chinese high school students, providing a tool for dynamic monitoring of health literacy among high school students and evaluating the effectiveness of health school construction.
Methods:
Through theoretical research, an evaluation index system for health literacy of Chinese high school students was constructed. Two rounds of Delphi expert consultations were conducted to quantitatively screen the items, and the item pool was revised based on expert opinions to compile the health literacy evaluation scale for Chinese students. Two focus group interviews were held to collect suggestions from health educators, high school teachers, and high school students regarding optimized scale length, question types, difficulty and wording of the scale. The scale was revised accordingly. A pilot survey was conducted in Beijing and Tianjin in November 2024, and the reliability and validity of the scale were evaluated based on the pilot survey data.
Results:
The response rate in both rounds of Delphi expert consultations was over 80%, and the expert authority coefficient was over 0.70. The expert opinions were highly concentrated, and the dispersion was small. The revised item pool based on expert opinions contained 39 items. The revised scale based on the suggestions and opinions collected from the focus group interviews had a moderate number of questions and difficulty level. The pilot survey obtained 800 valid responses, with the response rate of 89.39%. The Cronbach α coefficient of the scale was 0.911, χ 2/df =3.321, the root mean square error of approximation was 0.054, the adjusted goodness-of-fit index was 0.991 , and the factor loadings of some items were less than 0.40.
Conclusion
The health literacy evaluation scale for Chinese high school students demonstrates scientific rigor and practical applicability, with good internal consistency and structural validity.
8.Prognostic Value of MELD 3.0 Based Model for Survival Outcomes in Alcoholic Cirrhosis Patients
Zhenwei ZHONG ; Kodjo Kunale ABASSA ; Rong CHEN ; Yunwei GUO ; Bin WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):318-327
ObjectiveTo explore the value of the Model for End-Stage Liver Disease (MELD) 3.0 in predicting survival outcomes for patients with alcoholic cirrhosis and to establish an effective mortality prediction model. MethodsClinical data of 788 hospitalized patients who were first diagnosed with alcoholic cirrhosis at the Third Affiliated Hospital of Sun Yat-sen University between January 1, 2011 and December 31, 2019 were analyzed. Patients were followed up until December 31, 2023 and divided into survival and mortality groups based on the survival outcomes at 30 days, 90 days, 1 year, and 3 years after admission. The prognostic values of the MELD 3.0, MELD, MELD-Sodium (MELD-Na) for survival in alcoholic cirrhosis patients were assessed and compared by using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Additional risk factors associated with mortality in alcoholic cirrhosis patients were identified, and a novel mortality prediction model based on MELD 3.0 was developed. ResultsThe AUC of the MELD 3.0 score in predicting 30-day, 90-day, 1-year, and 3-year survival was 0.823, 0.730, 0.686, and 0.658, respectively, which were superior to those of the MELD-Na (0.802, 0.708, 0.666, and 0.645, respectively) and MELD scores (0.698, 0.668, 0.654, and 0.633, respectively) (all P < 0.05). MELD 3.0 demonstrated better performance at 30 and 90 days (AVC=0.823,0.730; both P < 0.05) than at 1 year and 3 years (AVC=0.686,0.658; both P < 0.05). Binary logistic regression combined with LASSO regression indicated that the independent risk factors associated with the 1-year outcome included MELD 3.0, baseline ascites and hepatocellular carcinoma. A survival prediction model was then established with AUC of 0.748, sensitivity of 0.695, and specificity of 0.775. ConclusionsMELD 3.0 has a superior predictive ability for 30-day, 90-day, 1-year, and 3-year survival in patients with alcoholic cirrhosis than MELD-Na and MELD. The prediction model incorporating MELD 3.0, ascites and hepatocellular carcinoma improves the prediction of 1-year survival outcomes for alcoholic cirrhosis patients.
9.Problems and countermeasures in palliative care education for medical students
Qiuju YANG ; Jiawei SONG ; Haowei ZHANG ; Di LIU ; Bin GUO
Chinese Medical Ethics 2025;38(7):937-942
Palliative care is a way to help end-of-life populations improve their quality of life, and its development in practice cannot be separated from the level of education in palliative care. At present, some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system, lack of medical students’ hospice knowledge; insufficient interdisciplinary teaching faculty, weak palliative care awareness of medical students; single teaching evaluation mode; weak palliative care practice teaching links. To this end, it is necessary to improve the palliative care curriculum system, explore rich and diverse teaching methods; strengthen interdisciplinary teaching and faculty development, enhancing the awareness of palliative care among medical students;establish a scientific and effective evaluation method, carry out multi-dimensional dynamic assessment; expand the palliative care practice teaching base, and accurately improve the practical skills of medical students in palliative care, and other countermeasures to improve the level of palliative care education, and to help the strategy of Healthy China.
10.Mechanism of Xiayuxue Tang in Inhibiting Hepatocellular Carcinoma Cells by Regulating YAP1/SIRT5 Signaling Axis to Mediate Succinate Metabolism and Succinylation
Linzhu LU ; Qianqian GUO ; Xuefei TIAN ; Bin CHEN ; Nianhua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):52-61
ObjectiveTo investigate the inhibitory effects and mechanisms of Xiayuxue Tang (XYXT) on hepatocellular carcinoma cells through the regulation of succinate metabolism and succinylation modification. MethodsXYXT-medicated serum was prepared. The effects of different concentrations of succinate on the proliferation of HepG2 and MHCC97H cells were observed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations for subsequent tests were determined. Further CCK-8 assays were performed to evaluate the effects of XYXT-medicated serum of different concentrations (5%, 10%, and 15%) on cell proliferation. Flow cytometry, scratch test, and Transwell assay were employed to analyze the effect of 10% XYXT-medicated serum on the cell cycle, migration, invasion, and apoptosis. The changes in succinate metabolism and succinylation modification were examined based on succinate content assays, succinate dehydrogenase (SDH) activity detection, and western blot. The expressions of Yes-associated protein 1 (YAP1) and sirtuin 5 (SIRT5) were detected via Real-time PCR and western blot. Molecular docking was applied to validate the binding between XYXT’s main components and target proteins. ResultsCompared with the control group, 1-2 mmol·L-¹ succinate significantly promoted HepG2 and MHCC97H cell proliferation (P<0.01). XYXT-medicated serum (5%, 10%, and 15%) markedly inhibited the proliferation of both cell lines compared with the blank group (P<0.05, P<0.01). Treatment with 10% XYXT-medicated serum arrested the cell cycle at the stage prior to DNA synthesis (G0/G1) (P<0.01), suppressed migration (P<0.01) and invasion (P<0.05, P<0.01), and promoted apoptosis of HepG2 and MHCC97H cells (P<0.01). Co-treatment with XYXT and succinate reversed the inhibitory effects of XYXT on proliferation, migration, and invasion of HepG2 and MHCC97H cells (P<0.05, P<0.01). The proportion of cells at G0/G1 phase decreased (P<0.01), and the apoptosis rate decreased (P<0.01). In terms of succinate metabolism, compared with the blank serum group, the 10% XYXT-medicated serum reduced succinate levels of HepG2 and MHCC97H cells (P<0.05, P<0.01), enhanced SDH activity (P<0.01), and downregulated succinylation modification. In terms of YAP1/SIRT5 pathway, compared with the blank serum group, the 10% XYXT-medicated serum significantly downregulated the mRNA and protein expressions of YAP1 in HepG2 and MHCC97H cells (P<0.05, P<0.01) while significantly upregulated the mRNA and protein expressions of SIRT5 (P<0.05, P<0.01). Molecular docking confirmed that there was a good binding ability between YAP1 and SIRT5, as well as between XYXT's main active components and YAP1 and SIRT5. ConclusionXYXT suppresses hepatocellular carcinoma cells by modulating the YAP1/SIRT5 signaling axis to intervene in succinate metabolism and succinylation modification.


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