1.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
2.Establishment and Application of Animal Models for Disease-syndrome Combination in Viral Pneumonia: A Review
Dan XIE ; Shuran LI ; Zihan GENG ; Lei BAO ; Jing SUN ; Ronghua ZHAO ; Xian LIU ; Mengyao CUI ; Xiaowei YANG ; Xiaolan CUI ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):61-69
Currently, viral pneumonia (VP) presents a major challenge to global public health. Traditional Chinese medicine (TCM) prevention and treatment of VP is guided by the core concept of strengthening vital energy and eliminating pathogenic factors rather than targeting specific pathogens, alongside a holistic approach of syndrome differentiation and treatment. By summarizing the clinical syndromes of patients, the core pathogenesis was clarified to achieve individualized therapy. Animal models for disease-syndrome combination integrate the etiology and pathogenesis of VP and simulate the individualized manifestations of patients at different disease stages, providing an experimental platform for elucidating the theoretical basis of TCM in treating VP and promoting the development of effective TCM formulations. However, there are limitations in the application and promotion of disease-syndrome combination animal models due to the lack of standardization and normalization of model construction systems, which arise from diverse species selection, compound modeling methods, and multidimensional evaluation indicators. This paper systematically reviewed the recent research on animal models for disease-syndrome combination in VP from the perspective of species selection, modeling methods, evaluation indicators, and application status. Furthermore, it summarized the advantages and limitations of existing models, identifies future directions for improvement, and proposes optimization strategies. This review provides a reference for establishing standardized and normalized animal models for disease-syndrome combinations in VP, supporting the theoretical modernization of TCM in preventing and controlling emerging respiratory infectious diseases, and contributing to the development of new TCM drugs.
3.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
4.Establishment and Application of Animal Models for Disease-syndrome Combination in Viral Pneumonia: A Review
Dan XIE ; Shuran LI ; Zihan GENG ; Lei BAO ; Jing SUN ; Ronghua ZHAO ; Xian LIU ; Mengyao CUI ; Xiaowei YANG ; Xiaolan CUI ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):61-69
Currently, viral pneumonia (VP) presents a major challenge to global public health. Traditional Chinese medicine (TCM) prevention and treatment of VP is guided by the core concept of strengthening vital energy and eliminating pathogenic factors rather than targeting specific pathogens, alongside a holistic approach of syndrome differentiation and treatment. By summarizing the clinical syndromes of patients, the core pathogenesis was clarified to achieve individualized therapy. Animal models for disease-syndrome combination integrate the etiology and pathogenesis of VP and simulate the individualized manifestations of patients at different disease stages, providing an experimental platform for elucidating the theoretical basis of TCM in treating VP and promoting the development of effective TCM formulations. However, there are limitations in the application and promotion of disease-syndrome combination animal models due to the lack of standardization and normalization of model construction systems, which arise from diverse species selection, compound modeling methods, and multidimensional evaluation indicators. This paper systematically reviewed the recent research on animal models for disease-syndrome combination in VP from the perspective of species selection, modeling methods, evaluation indicators, and application status. Furthermore, it summarized the advantages and limitations of existing models, identifies future directions for improvement, and proposes optimization strategies. This review provides a reference for establishing standardized and normalized animal models for disease-syndrome combinations in VP, supporting the theoretical modernization of TCM in preventing and controlling emerging respiratory infectious diseases, and contributing to the development of new TCM drugs.
5.Current status and suggestions on regulation of traditional Chinese medicine raw materials and preparations under regulatory system of drugs.
Li-Ping QU ; Yong-Dan XU ; Wei-Jing HE ; Ding-Kun ZHANG ; Nan YANG ; Min-Xian SONG ; Zhi-Qiang MIN ; Ting-Mo ZHANG
China Journal of Chinese Materia Medica 2025;50(3):824-832
At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics*
;
Medicine, Chinese Traditional/standards*
;
China
;
Quality Control
;
Humans
;
Plants, Medicinal/chemistry*
6.Bioinformatics analysis of efferocytosis-related genes in diabetic kidney disease and screening of targeted traditional Chinese medicine.
Yi KANG ; Qian JIN ; Xue-Zhe WANG ; Meng-Qi ZHOU ; Hui-Juan ZHENG ; Dan-Wen LI ; Jie LYU ; Yao-Xian WANG
China Journal of Chinese Materia Medica 2025;50(14):4037-4052
This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans
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Computational Biology
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Diabetic Nephropathies/physiopathology*
;
Protein Interaction Maps
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Medicine, Chinese Traditional
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Drugs, Chinese Herbal
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Phagocytosis/genetics*
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Efferocytosis
7.Effect of Bushen Huoxue Granule on Clearance of Pathological α-Synuclein in MPP+-Induced PC12 Cells.
Zhen-Xian LUAN ; Xiang-Lin TANG ; Fei-Ran HAO ; Min LI ; Shao-Dan LI ; Ming-Hui YANG
Chinese journal of integrative medicine 2025;31(9):830-836
OBJECTIVE:
To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease.
METHODS:
After treated with 1-methyl-4-phenylpyridinium (MPP+, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay.
RESULTS:
BCS (volume fraction ⩽20%) intervention could alleviate the MMP+-induced cell viability decrease (P<0.05). In the MPP+ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP+-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP+-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05).
CONCLUSION
BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP+ in the in vitro model of Parkinson's disease.
PC12 Cells
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alpha-Synuclein/metabolism*
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Rats
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Animals
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1-Methyl-4-phenylpyridinium/toxicity*
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Proteasome Endopeptidase Complex/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
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Ubiquitin/metabolism*
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Cell Survival/drug effects*
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Phosphorylation/drug effects*
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Tyrosine 3-Monooxygenase/metabolism*
8.Application of quality control circle in reducing the surface extravasation rate of"bolus-type"intravenous injection of radiopharmaceuticals
Yuxian ZHANG ; Dan KONG ; Weiying LIU ; Jialang XIAN
Journal of Practical Radiology 2024;40(12):2062-2065
Objective To explore the role of quality control circle in reducing the rate of extravasation during"bolus-type"intravenous injection of radiopharmaceuticals.Methods A total of 624 patients who underwent emission computed tomography(ECT)examinations were retrospectively selected as the pre-quality control circle use analysis group,125 patients who underwent ECT examinations were selected as the post-quality control circle use experiment group,and 70 patients were selected as the control group.This study applied the continuous quality improvement tools of the quality control circle,including grasping the current situation,selecting injection tools,personnel training,brainstorming,root cause analysis,key factor evaluation,true cause verification,strategy formulation and measure implementation,to continuously improve the quality of"bolus-type"radioisotope injection and reduce the rate of radiopharmaceuticals extravasation.Results In the experiment group,the rate of radioisotope extravasation after nurses performed"bolus-type"intravenous injection was 14.2%,compared to 33.3%in the control group,an improvement of 19%,and the situation of radiopharmaceuticals extravasation was significantly improved.Skillful use of quality improvement tools,especially in areas such as insufficient compression time,improper compression method,slow blood flow speed in fine blood vessels,and failed puncture,was crucial for radioisotope sur-face imaging.Conclusion Through continuous quality improvement by the quality control circle,this study successfully reduces the rate of extravasation during"bolus-type"intravenous injection of radiopharmaceuticals,reduces skin contamination,and improves the quality of nuclear medicine images,which is of great significance for improving the safety and diagnostic accuracy of nuclear medicine ECT examinations.
9.Clinical Observation on Comprehensive Traditional Chinese Medicine Therapy in Treating Refractory Sudden Hearing Loss
Qi XIAO ; Dan-Hui ZHANG ; Peng LIU ; Wei-Zhe HONG ; Wei-Ping HE ; Hua-Min GUO ; Hui-Xian XU ; Jing LIU ; En-Qin GUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1486-1492
Objective To observe the curative effect of comprehensive traditional Chinese medicine(TCM)therapy for the treatment of refractory sudden hearing loss(i.e.,suffering sudden hearing loss more than 2 weeks),and to analyze the factors that may affect the prognosis.Methods A retrospective analysis was carried out in 405 hospitalized patients with refractory sudden hearing loss who were treated in the Department of Otorhinolaryngology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2005 to 2022.The patients were all treated by comprehensive TCM therapy including oral administration of Chinese medicine,acupuncture,acupoint seed-pressing application after individualized syndrome differentiation.The overall clinical efficacy was evaluated,and the difference of efficacy in the patients with various courses of disease,degrees of deafness,types of hearing curve,concomitant symptoms and TCM syndrome types,having or not having previous treatment history was analyzed.Results For the 405 patients with refractory sudden hearing loss,the cure rate was 5.7%and the total effective rate was 28.1%.Among the 405 patients,the best efficacy was achieved in the patients with mild hearing loss,low-frequency decline type of hearing curve,and having no previous treatment history,and the differences were statistically significant(P<0.05 or P<0.01).There was no significant difference in the efficacy of patients with different courses of disease,with or without concomitant symptoms,or with various syndrome types(P>0.05).Conclusion The comprehensive TCM therapy has a certain effect on refractory sudden hearing loss.Patients with poor efficacy after conventional western medicine can still benefit from the comprehensive TCM therapy.
10.Effects of total saponins of Trillium tschonoskii Maxim on cognitive function and neurovascular unit in 2-VO model rats
Dan YANG ; Li-Jun YANG ; Xian-E TANG ; Gang WANG ; Ren-Ze DUAN ; Xian-Bing CHEN
Medical Journal of Chinese People's Liberation Army 2024;49(3):316-322
Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P<0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P<0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P<0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P<0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P<0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P<0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.

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