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.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

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.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans ; Carcinoma, Renal Cell/therapy* ; Immunotherapy ; Glycolysis ; Metabolic Reprogramming ; Kidney Neoplasms/therapy* ; Tumor Microenvironment

Objective: To investigate cardiovascular disease (CVD) prevention status among residents with intra-urban migration in Central China, so as to provide insights into targeted prevention and control of CVD. Methods: Basic data of residents aged 35 to 75 years who participated in Early Screening and Comprehensive Intervention Project for CVD high-risk populations in Central China from September 2015 to August 2020 were collected. According to birth place, type of registered residence and current residence, residents were divided into four groups: local residents in old urban area, local residents in new urban area, other urban migrants and other rural migrants. The status of CVD primary and secondary prevention, were analysed by using a robust Poisson regression model. Results: A total of 76 513 residents were recruited, including 29 420 males (38.45%) and 47 093 females (61.55%), and had a mean age of (56.36±9.84) years. There were 45 087 (58.93%) local residents in old urban area, 23 868 (31.19%) local residents in new urban area, 5 668 (7.41%) other urban migrants and 1 890 (2.47%) other rural migrants. After adjusting for variables such as age, gender and educational level, the results of robust Poisson regression analysis showed that compared with local residents in old urban area, local residents in new urban area had lower compliance rates of non- or moderate-drinking (RR=0.987, 95%CI: 0.975-1.000) and healthy diet (RR=0.535, 95%CI: 0.365-0.782), lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.616, 95%CI: 0.511-0.741), lower awareness (RR=0.873, 95%CI: 0.782-0.974) and control rates (RR=0.730, 95%CI: 0.627-0.849) of hypertension; other urban migrants had higher compliance rate of non-smoking (RR=1.045, 95%CI: 1.017-1.075); other rural migrants had lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.826, 95%CI: 0.707-0.966). Conclusion The CVD primaryprevention among local residents in new urban area is relatively poor among four groups of residents in Central China, and key interventions are needed.

Objective To investigate the association between metabolic associated fatty liver disease(MAFLD)and carotid atherosclerotic plaque.Methods A total of 1 107 patients who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from July,2014 to December,2022 were enrolled,and all patients underwent abdominal ultrasound and CT angiography of the head and neck arteries.Baseline data and clinical diagnosis were collected,and the patients were divided into MAFLD group with 499 patients and non-MAFLD group with 608 patients based on medical history,clinical tests,and imaging findings.According to the CT value,carotid plaques were classified into calcified plaques,non-calcified plaques,and mixed plaques.According to the NASCET criteria,carotid stenosis was categorized as normal vessel,slight stenosis,mild stenosis,moderate stenosis,and severe stenosis/occlusion.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for carotid atherosclerosis.Results Compared with the non-MAFLD group,the MAFLD group had a significantly higher proportion of patients with calcified plaques(74.3%vs 63.3%,P<0.05),non-calcified plaques(27.1%vs 17.1%,P<0.05),or mixed plaques(27.3%vs 20.7%,P<0.05),as well as a significantly higher proportion of patients with mild stenosis(50.9%vs 44.9%,P<0.05),moderate stenosis(14.6%vs 8.4%,P<0.05),or severe stenosis/occlusion(6.6%vs 3.5%,P<0.05).The univariate logistic regression analysis showed that MAFLD was a risk factor for calcified carotid plaques,non-calcified plaques,and mixed plaques,and it was also a risk factor for mild stenosis,moderate stenosis,and severe stenosis/occlusion of the carotid artery(all P<0.05).After adjustment for confounding factors,the multivariate Logistic regression analysis showed that MAFLD was an independent risk factor for calcified plaque,non-calcified plaque,mixed plaque,and moderate stenosis of the carotid arteries(all P<0.05).Conclusion MAFLD is an independent risk factor for moderate stenosis,calcified plaques,non-calcified plaques,and mixed plaques of the carotid arteries.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.