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.

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.

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.

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.

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.

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.

Pelvic floor muscle training (PFMT) is the first-line intervention for non-surgical treatment of female patients with stress urinary incontinence (SUI). However, due to the particularity of the physiological position of the pelvic floor muscles, 13% to 53% of patients are unable to perform PFMT correctly after the initial visit. In view of this, scholars at China and abroad put forward some other sports rehabilitation methods and achieve good clinical results. In this paper, exercise rehabilitation methods for female SUI patients were reviewed, including PFMT, core muscle training, Pilates, yoga, physical activities, etc., in order to provide reference for medical personnel to formulate scientific and feasible exercise rehabilitation programs for female SUI patients.

ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized， open， parallel controlled， and multi-center clinical study was conduted. Children with acute bronchitis （syndrome of phlegm-heat obstructing lung） were randomly assigned to an observation group and a control group. The control group received routine basic treatment， and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment， the clinical efficacy， TCM efficacy， time to symptom disappearance， time to cough disappearance， and clinical safety were compared between the two groups. ResultA total of 248 children were included （124 in the observation group and 124 in the control group）. After 7 days of treatment， the total response rate in terms of clinical efficacy in the observation group was 96.8% （120/124）， which was higher than that （90.3%， 112/124） in the control group （Z=-5.034， P<0.01）. The total response rate in terms of TCM syndrome in the observation group was 97.6% （121/124）， which was higher than that （93.5%， 116/124） in the control group （χ²=-5.326， P<0.01）. The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days （P<0.01）. The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group （P<0.01）. Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms， with high safety， which is worthy of clinical application and promotion.

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.

Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.