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.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
3.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.
4.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.
5.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
6.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.
7.Host Targets Interacting with Influenza Virus NP and Mechanism of Gardenia Jasminoides Iridoid Glycoside Against Influenza Virus
Xiaowei YANG ; Lei BAO ; Yu ZHANG ; Xian LIU ; Zihan GENG ; Shuran LI ; Jingsheng ZHANG ; Xiaolan CUI ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):60-66
ObjectiveTo explore host factors interacting with influenza virus nucleoprotein (NP) and study their effects on influenza virus replication, as well as the mechanism of gardenia jasminoides iridoid glycoside (IGE) in inhibiting influenza virus. MethodA yeast two-hybrid system was utilized to screen host factors that interacted with influenza virus NP. Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD), glucosamine-6-phosphate deaminase 1 (GNPDA1), poly(rC)-binding protein 1 (PCBP1), and protein inhibitor of activated signal transducer and activator of transcription (STAT) protein 1 (PIAS1) were validated by immunoprecipitation assay. The effects of PIAS1 and HNRNPD on influenza virus replication were compared by a dual luciferase assay, and the effects of IGE on influenza virus replication were examined in the presence of transfected ribonucleoprotein (RNP) and knockdown of PIAS1. ICR mice were randomly divided into a normal group, model group, oseltamivir phosphate group, and high, medium, and low dose IGE groups, with 10 mice in each group. In addition to the normal group, each group was infected with the influenza A virus FM1 strain by nasal drip to establish a viral pneumonia model. The high, medium, and low dose IGE groups were given drugs of 50, 25, and 12.5 mg∙kg-1 by gavage, and the oseltamivir phosphate group was given the drug of 27.5 mg∙kg-1 by gavage. Equal amounts of distilled water were instilled in the normal and model groups for four consecutive days. Later, protein expression of PIAS1, NP, phosphorylated (p)-STAT3, STAT3, p-STAT1, and STAT1 were detected in the lung tissue by Western blot. ResultIn yeast two-hybrid assays, 16 potential host targets interacting with influenza virus NP were identified. Immunoprecipitation experiments revealed that HNRNPD and PIAS1 could interact with influenza virus NP. The dual luciferase reporter assays found that both PIAS1 knockdown and overexpression significantly affected IAV RNP activity (P<0.05, P<0.01), and the effect of HNRNPD on IAV RNP was not significant. Both high and low dose IGE groups reduced influenza virus replication (P<0.05) and reversed the increase in influenza virus replication caused by the knockdown of PIAS1(P<0.05, P<0.01). The expressions of PIAS1, NP, p-STAT3, p-STAT1, and STAT1 in the lung tissue of infected mice were reduced to different degrees in each IGE group (P<0.05, P<0.01). ConclusionPIAS1 interacts with influenza virus NP and is able to inhibit influenza virus replication. IGE may exert antiviral effects by inhibiting the activity of IAV RNP through the PIAS1/STAT1 pathway.
8.Mixed urinary incontinence: can pelvic floor ultrasonography predict the success of retropubic midurethral synthetic sling?
Wenxin XU ; Jiayi LI ; Qixiang SONG ; Lei XU ; Yiyuan GU ; Yunyue GUO ; Xiaowei SUN ; Wei XUE
Journal of Modern Urology 2024;29(12):1069-1073
[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.
9.Drug prophylaxis evidence-based regimens for venous thromboembolism after joint replacement
Xiaowei FENG ; Na GUO ; Baozhen WANG ; Jie CHENG ; Yuchen TANG ; Jun QI ; Zhiqiang DONG
China Pharmacy 2024;35(22):2799-2807
OBJECTIVE To sort out drug prophylaxis regimens for venous thromboembolism (VTE) in adult patients after artificial joint replacement, and provide a basis for clinic. METHODS Databases and related official websites were searched according to the “6S” model, including the National Institute for Health and Clinical Excellence (NICE), the Scottish Intercollegiate Guidelines Network (SIGN), the Guidelines International Network (GIN), the National Guidelines Clearinghouse (NGC), PubMed, Embase, CNKI, Wanfang database and SinoMed, to search for guidelines, expert consensuses, systematic evaluations, randomized controlled trials, and cohort studies about preventing VTE in adult patients after artificial joint replacement from the inception until December 2023. Literature that met the inclusion criteria were selected, and the quality evaluation of the literature was completed by 2 researchers independently; the evidence rating was performed by using the Joanna Briggs Institute (JBI) evidence pre-classification and evidence rank system (2014 edition). RESULTS A total of 36 articles were included in the study, which were categorized into 9 areas of risk assessment, post-assessment prophylaxis, medication selection, medication method, duration of medication prophylaxis, medication prophylaxis observation points, contraindications to drug prophylaxis, response to bleeding, and health education, which were summarized to form 37 pieces of evidence on the pharmacological prophylaxis for postoperative VTE in patients who underwent artificial joint replacement. CONCLUSIONS The evidence of drug prophylaxis for postoperative VTE in patients who underwent artificial joint replacement summarized in this study is comprehensive, with certain scientific reference and practicality, which can provide clinical pharmacists with a scientific evidence-based basis for perioperative VTE prophylaxis management.
10.Progress in research into the Masquelet technique for chronic osteomyelitis of limbs
Yanhui GUO ; Xianyong MENG ; Hongying HE ; Li HAN ; Qing LI ; Xiaowei WANG ; Jianzheng ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(7):636-639
Masquelet technique has become a safe and effective treatment for chronic osteomyelitis of the long limb shaft. The vast majority of osteomyelitis can be ultimately controlled, segmental bone defects repaired and limb functions restored. Accumulation of clinical applications and development of imaging technology have led to rapid progress in determining the infection scope of chronic limb osteomyelitis, precise preoperative design for repair of soft tissue defects, evaluation of bone structure stability, and use of bone grafting materials. This article reviews the progress of Masquelet technique in the treatment of chronic limb osteomyelitis from the aspects of its theoretical foundation, key operations, and selection of fixation methods, hoping to deepen the understanding of current Masquelet technique.

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