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.Application of CXCR4-targeted PET/CT imaging in the classification and precise localization of primary aldosteronism
Xuan YIN ; Xiaowei MA ; Chuning DONG ; Lianbo ZHOU ; Rongchen AN ; Honghui GUO ; Xin XIANG ; Xinlu ZHANG ; Hong XIANG ; Yunhua WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):76-81
Objective:To investigate the application value of 68Ga-Pentixafor PET/CT targeting CXC subfamily receptor 4 (CXCR4) in the subtyping and precise localization of primary aldosteronism (PA). Methods:Thirty-three patients with PA confirmed by clinical examination and undergoing 68Ga-Pentixafor PET/CT and adrenal vein sampling (AVS) in the Second Xiangya Hospital between July 1st 2022 and July 1st 2023 were prospectively enrolled (24 males, 9 females, age (49.6±10.3) years). Patients with a dominant side identified by PET/CT or AVS underwent unilateral adrenalectomy, while those without a dominant side received medical treatment. According to the standard of PA surgical outcome (PASO), patients underwent surgery were divided into unilateral PA (UPA) and bilateral PA (BPA) based on the pathological and follow-up results. Those who received medical treatment were BPA. The diagnostic efficacy of 68Ga-Pentixafor PET/CT for UPA was calculated. The ROC curve was constructed to analyze the accuracy and optimal threshold of SUV max, the ratio of lesion SUV max to contralateral adrenal tissue SUV mean (LCR), and the ratio of lesion SUV max to liver SUV mean (LLR) in the diagnosis of PA subtype. The correlation between the quantitative parameters and the clinical features and lesion width of the patients was evaluated by Spearman rank correlation analysis. The differences of LCR and LLR between different efficacy groups were compared by the independent-sample t test. Results:A total of 20 patients underwent unilateral adrenalectomy. Nineteen patients were finally diagnosed with UPA and 14 with BPA. The agreement rate of PET/CT and AVS was 81.8%(27/33), and both methods independently detected UPA that was negative in the other examination. The sensitivity, specificity, and accuracy of 68Ga-Pentixafor PET/CT visual diagnosis of UPA were 18/19, 14/14, and 97.0%(32/33), respectively. ROC curve showed that the AUC of LLR for subtype diagnosis was 0.944, with the optimal threshold of 3.1. SUV max, LCR, and LLR were positively correlated with aldosterone concentration ( rs values: 0.35, 0.47, and 0.36, all P<0.05) and lesion width ( rs values: 0.43, 0.49, and 0.58, all P<0.05). The LCR (3.9±2.2 vs 1.6±0.3; t=2.00, P=0.041) and LLR( 8.7±4.1 vs 4.2±1.3; t=2.06, P=0.045) of the dominant side lesions in patients who achieved complete biochemical and clinical cure were higher than those in patients with partial improvement. Conclusions:68Ga-Pentixafor PET/CT imaging can be used in the diagnosis and precise localization of PA subtype. It also can detect patients with PA which can be surgically cured but not detected by AVS, and the quantitative analysis may be valuable for prognosis prediction.
8.Analysis of the results of external quality control for EBER in situ hybridization in 38 laboratories
Qing CAI ; Wenyang GUO ; Xiaowei XUE ; Detian WANG ; Xianbo WANG ; Weixun ZHOU
Chinese Journal of Clinical and Experimental Pathology 2025;41(7):918-923
Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74%(36/38),and the excellent& good rate was 26.32%(10/38).The excellent & good rate of automated staining(41.12%,7/17)was significant-ly higher than that of manual staining(14.29%,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.
9.Comparison of prognosis between liver resection and transarterial chemoembolization in patients with Budd-Chiari syndrome complicating hepatocellular carcinoma
Zedong WANG ; Suxin LI ; Luhao LI ; Zhaochen LIU ; Lin LI ; Huahu GUO ; Yang YANG ; Shuaibo LING ; Shengyan LIU ; Xiaowei DANG
Chinese Journal of General Surgery 2025;40(5):360-365
Objective:To explore the prognostic differences between liver resection and transarterial chemoembolization (TACE) in patients with Budd-Chiari syndrome (BCS) complicated by hepatocellular carcinoma (HCC) and to identify independent risk factors affecting patient survival.Methods:The clinical and follow-up data of 103 patients with stage Ⅰa-Ⅲa BCS complicated by HCC treated at the First Affiliated Hospital of Zhengzhou University from Aug 2015 to Sep 2023 were retrospectively analyzed.Results:Patients were divided into two groups based on their initial treatment choices: the liver resection group ( n=20) and the TACE group ( n=83). Before propensity score matching(PSM), the median overall survival in the liver resection group was 42 months longer than in the TACE group (74 months vs. 32 months, P=0.002). After PSM, the median overall survival remained significantly longer in the liver resection group by 39 months (74 months vs. 35 months, P=0.032). In terms of disease-free survival, before PSM, the liver resection group was 30-month longer than the TACE group (42 months vs. 12 months, P=0.001). After PSM, the difference in median disease-free survival between the two groups was 23 months (35 months vs. 12 months, P=0.018). Multivariate Cox regression analysis identified treatment modality and maximum tumor diameter as independent risk factors for overall survival, while treatment modality was the only independent factor for disease-free survival. Conclusions:Liver resection significantly prolongs both overall survival and disease-free survival in resectable HCC in BCS patients compared to TACE. Treatment modality and tumor size are key prognostic factors influencing overall survival.
10.Development and validation of the Body Image Flexibility Questionnaire for Middle School Students
Ruichao JIAO ; Dan ZHENG ; Xiaowei GUO ; Dongdong XUE ; Qin WANG ; Xiaozhuang WANG
Chinese Mental Health Journal 2025;39(6):515-521
Objective:To develop the Body Image Flexibility Questionnaire for Middle School Students(BIFQ-MS)and test its validity and reliability.Methods:Firstly,the initial questionnaire was developed based on the hexaflex model of psychological flexibility.Secondly,701 middle school students were selected to complete the initial questionnaire for item analysis and exploratory factor analysis.Thirdly,899 middle school students were ex-amined to conduct confirmatory factor analysis,criterion-related validity and internal consistency tests on the formal questionnaire.The Body Image-Acceptance and Action Questionnaire(BI-AAQ),Avoidance and Fusion Question-naire for Youth(AFQ-Y8),Body Areas Satisfaction Scale(BASS),and General Appearance subscale of the Nega-tive Physical Self Scale(NPSS-GA)were used to test criterion validity.In addition,88 middle school students were retested 4 weeks later.Results:The BIFQ-MS consisted of 26 items,including 4 factors(openness to experience,self-as-context,contact with the present moment,and valued action),which explained 65.55%of the total vari-ance.Confirmatory factor analysis showed that the four-factor structural model fitted well(x2/df=2.26,CFI=0.97,TLI=0.97,RMSEA=0.04,SRMR=0.03).The BIFQ-MS total scores and the scores of each factor were positively correlated with the scores of the BI-AAQ and the BASS(r=0.41-0.50,Ps<0.01),whereas they were negatively correlated with the scores of the NPSS-GA and the AFQ-Y8(r=-0.28--0.58,Ps<0.01).The Cronbach's α coefficients of the total questionnaire and the 4 factors ranged from 0.91 to 0.97,and the test-retest reliabilities(ICC)ranged from 0.70 to 0.86.Conclusion:The Body Image Flexibility Questionnaire for Middle School Students is a reliable tool for understanding body image flexibility in adolescents.

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