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.

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.

[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.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Objective:To examine the effect of short-term regular aerobic exercise on physical fitness of children with pulmonary with atresia ventricular septal defect after radical biventricular treatment.Methods:This was a prospective self pre-and post-control observation study. The subjects performed regular aerobic exercise for 10 days according to the exercise prescription. Body composition measurement and cardiopulmonary exercise test[lung ventilation function, maximum oxygen uptake(VO 2max), maximum oxygen pulse(O 2/HR max), ventilation oxygen uptake efficiency(OUES), exercise load time], 6 min walking distance(6MWD), sports psychometric test, motor function screening test and fitness test, were collected. The changes of test parameters and scale scoring before and after exercise were analyzed and compared. Results:A total of 7 children with PA/VSD after biventricular surgery were enrolled. The age ranged 8.2-16.2 years old, and there were 2 males and 5 females. VO 2max[(1 196.71±395.31)ml/min vs.(1 297.43±425.73)ml/min, P=0.031], O 2/HRmax[(82.43±7.53)ml/beat vs.(91.57±6.95)ml/beat, P<0.001]increased after exercise. The exercise load time was significantly increased compared with that before intervention[(476.43±35.73)s vs.(531.43±45.76)s, P=0.002]. Resting heart rate before exercise( P=0.013) and peak respiration exchange ratio(PeakRER, P=0.021) were significantly lower. Body composition tests suggest weight, intracellular water, protein and muscle content of lower limb were higher( P<0.05). The motor function score was higher than before( P=0.015); the score of sports fear was lower than before( P=0.009). There was no significant difference in lung capacity and 6-minute walking distance before and after exercise( P>0.05). There were no cardiovascular events during the study period. Conclusion:Short-term regular aerobic exercise for children with PA/VSD after biventricular surgery can improve exercise tolerance, increase lower limb muscle content, improve exercise fear and exercise function, and has good safety and feasibility.