1.Accuracy of large language models for answering pediatric preventive dentistry questions
GUAN Boyan ; XU Minghe ; ZHANG Huiqi ; MA Shulei ; ZHANG Shanshan ; ZHAO Junfeng
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(4):313-319
Objective:
To evaluate and compare the accuracy of responses to pediatric preventive dentistry-related questions between the domestic large language model, ChatGLM-6B, and the international large language model, ChatGPT-3.5, in order to provide insights for further research and development of domestic language models in the field of oral medicine.
Methods:
A total of 100 common pediatric preventive dentistry questions of varying difficulty levels [basic (n = 35), intermediate (n = 35), and advanced (n = 30) ] were provided by pediatric preventive dentistry experts. Two doctors independently registered these questions with ChatGPT-3.5 and ChatGLM-6B and collected the answers. A cohort of 16 dentists assessed responses generated by ChatGLM-6B and ChatGPT-3.5 using a predefined 3-point Likert scale. The average score of the ratings from 16 doctors was taken as the answer score. If the answer score was higher than 2.8, it was accepted as a accurate answer; if the score was lower than 1.4, it was accepted as an inaccurate answer; if the score was between 1.4 and 2.8, it was accepted as a partially accurate answer. Comparative analysis was conducted on the accuracy rates and evaluation outcomes between the two groups. Consistency analysis of the ratings was conducted
Results:
The answer accuracy rates of ChatGPT-3.5 and ChatGLM-6B for 100 pediatric preventive dentistry questions were comparable: ChatGPT-3.5 demonstrated 68% accurate, 30% partially accurate, and 2% inaccurate responses, while ChatGLM-6B showed 67% accurate, 31% partially accurate, and 2% inaccurate responses, with no statistically significant differences (P>0.05). Both models exhibited equivalent accuracy across questions of varying difficulty levels (basic, intermediate, advanced), showing no statistical differences (P>0.05). The overall average scores for ChatGPT3.5 and ChatGLM-6B in answering all questions were both 2.65, with no statistically significant difference (P>0.05). For questions of different difficulty levels, ChatGPT3.5 had an average score of 2.66 for basic questions while ChatGLM-6B had an average score of 2.70. For intermediate questions, ChatGPT3.5 had an average score of 2.63 and ChatGLM-6B had an average score of 2.64. For advanced questions, ChatGPT3.5 had an average score of 2.68, and ChatGLM-6B had an average score of 2.61. No statistically significant differences were observed across any difficulty category (P>0.05). The consistency of the experts’ grading ranged from fair to moderate.
Conclusion
This study demonstrates the potential of both ChatGLM-6B and ChatGPT-3.5 in answering pediatric preventive dentistry questions. ChatGLM-6B performed similarly to ChatGPT-3.5 in this field, but the accuracy rates of both models fell short of expectations and are not suitable for clinical use. Future efforts should focus on improving the accuracy and consistency of large language models in providing medical information, as well as developing specialized medical models for the field of oral medicine.
2.Cost-effectiveness of vitamin D analogue for postmenopausal osteoporosis in women
Haijing GUAN ; Yanan XU ; Zhigang ZHAO ; Changsheng FAN
China Pharmacy 2025;36(10):1209-1215
OBJECTIVE To evaluate the cost-effectiveness of vitamin D analogue for postmenopausal osteoporotic women in China. METHODS A Markov microsimulation model was developed to analyze the clinical and economic outcomes of eldecalcitol, alfacalcidol and calcitriol for postmenopausal osteoporosis from the healthcare system perspective in China. The clinical parameters required for the model were derived from network meta-analysis, while cost and utility data were primarily obtained from the literature. The cycle length was 1 year , the time horizon was life time, and the willingness-to-pay threshold was 0.5 times the gross domestic product per capita in China in 2023(44 679 yuan/QALY). Model uncertainty was tested with one-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis. RESULTS The quality-adjusted life years (QALYs) for eldecalcitol were calculated to be 12.03 QALYs, which were higher than those for alfacalcidol (11.94 QALYs) and calcitriol (11.92 QALYs). Meanwhile, the direct medical cost associated with eldecalcitol treatment amounted to 38 805 yuan, which was lower than that of alfacalcidol (45 173 yuan) and calcitriol (45 821 yuan). The results of the one-way sensitivity analysis showed that the risk ratio of hip fracture and vertebral fracture had a significant impact on the result. The probabilistic sensitivity analysis and scenario analysis showed the robustness of the findings from the base-case analysis. CONCLUSIONS Compared with alfacalcidol and calcitriol, eldecalcitol is likely to be a cost-effective treatment for postmenopausal osteoporotic women in China.
3.Association between serum creatinine/cystatin C ratio and nonalcoholic fatty liver disease in adults
Qizhen ZHANG ; Sutong LIU ; Lihui ZHANG ; Yajie GUAN ; Junjiao XU ; Wenxia ZHAO ; Minghao LIU
Journal of Clinical Hepatology 2025;41(6):1083-1089
ObjectiveTo investigate the association between serum creatinine/cystatin C ratio (CCR) and nonalcoholic fatty liver disease (NAFLD) based on the NHANES database, and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999 — 2004, a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups, and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD; CCR was divided into 4 groups based on quartiles, and odds ratio (OR) and 95% confidence interval (CI) in the regression model was calculated with the first quartile as reference. In addition, the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD, and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group (Z=-4.76,P<0.01). The Logistic regression analysis showed that in model 1 without adjustment of variables, CCR was negatively associated with NAFLD (OR=0.993,95%CI:0.989 — 0.996,P<0.01), and in model 3 with adjustment of all variables, CCR was still negatively associated with NAFLD (OR=0.986,95%CI:0.981 — 0.991,P<0.01). The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3, compared with the individuals with the lowest quartile of CCR, the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD (OR=0.426,95%CI:0.316 — 0.574,P<0.01). Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance (Pinteraction<0.01 and Pinteraction=0.04). The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population (≤60 years) (OR=0.982,95%CI:0.976 — 0.987), and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women (OR=0.979,95%CI:0.972 — 0.986). ConclusionThis study shows a significant negative association between CCR and NAFLD, and such association is more significant in middle-aged individuals and women.
4.Establishment and Evaluation of Insomnia Animal Models with Heart and Spleen Deficiency
Jieyao DIAO ; Hui XU ; Yunfeng ZHOU ; Zhen WANG ; Xin ZHAO ; Haoguang QU ; Chongyang GUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):234-243
Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model, this paper used multiple databases to search for the keywords "heart and spleen deficiency", "insomnia", "sleepless", "disease syndrome-combined animal model", "model evaluation", etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment, modeling factors, syndrome model, disease model, macro characterization & macro characterization evaluation scale, micro indicators, etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method, the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease, and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation, which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine (TCM) syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome, along the specific related ideas of "prescription and syndrome, treatment principle and selection of prescription, treatment principle and selection of acupoints, as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice, so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.
5.Establishment and Evaluation of Insomnia Animal Models with Heart and Spleen Deficiency
Jieyao DIAO ; Hui XU ; Yunfeng ZHOU ; Zhen WANG ; Xin ZHAO ; Haoguang QU ; Chongyang GUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):234-243
Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model, this paper used multiple databases to search for the keywords "heart and spleen deficiency", "insomnia", "sleepless", "disease syndrome-combined animal model", "model evaluation", etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment, modeling factors, syndrome model, disease model, macro characterization & macro characterization evaluation scale, micro indicators, etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method, the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease, and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation, which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine (TCM) syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome, along the specific related ideas of "prescription and syndrome, treatment principle and selection of prescription, treatment principle and selection of acupoints, as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice, so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.
6.Cost-effectiveness of angiographic quantitative flow ratio-guided coronary intervention: A multicenter, randomized, sham-controlled trial.
Yanyan ZHAO ; Changdong GUAN ; Yang WANG ; Zening JIN ; Bo YU ; Guosheng FU ; Yundai CHEN ; Lijun GUO ; Xinkai QU ; Yaojun ZHANG ; Kefei DOU ; Yongjian WU ; Weixian YANG ; Shengxian TU ; Javier ESCANED ; William F FEARON ; Shubin QIAO ; David J COHEN ; Harlan M KRUMHOLZ ; Bo XU ; Lei SONG
Chinese Medical Journal 2025;138(10):1186-1193
BACKGROUND:
The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system.
METHODS:
This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China.
RESULTS:
At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained.
CONCLUSION:
In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT03656848.
Humans
;
Cost-Benefit Analysis
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Percutaneous Coronary Intervention/methods*
;
Male
;
Female
;
Coronary Angiography/methods*
;
Middle Aged
;
Aged
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Coronary Artery Disease/surgery*
;
Quality-Adjusted Life Years
;
Fractional Flow Reserve, Myocardial/physiology*
7.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
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Perfusion/methods*
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Disease Models, Animal
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Brain Injuries/etiology*
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Swine
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Male
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Hypothermia, Induced/methods*
8.The PGAM5-NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis.
Cheng-Long GAO ; Jinqian SONG ; Haojie WANG ; Qinghong SHANG ; Xin GUAN ; Gang XU ; Jiayang WU ; Dalei WU ; Yueqin ZHENG ; Xudong WU ; Feng ZHAO ; Xindong LIU ; Lei SHI ; Tao PANG
Acta Pharmaceutica Sinica B 2025;15(1):349-370
The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.
9.Protective mechanism of amifostine on acute radiation injury by regulating gut microbiota
Yue CONG ; Li LI ; Yimeng ZHAO ; Yuanyuan XU ; Jianting GONG ; Jiali GUAN
China Pharmacy 2024;35(4):459-463
OBJECTIVE To explore the protective mechanism of amifostine on acute radiation injury mice. METHODS Thirty C57BL/6J mice were randomly divided into normal control group, model group and amifostine group (150 mg/kg), with 10 mice in each group. Thirty minutes before irradiation, the mice in the amifostine group were intraperitoneally injected with amifostine; normal control group and model group were given constant volume of normal saline intraperitoneally; then acute radiation injury was induced by 4 Gy X-ray radiation in both model group and amifostine group. The white blood cell count (WBC), platelet count and red blood cell (RBC) count in mice were detected 2 hours before irradiation and on days 1, 4, 7, 10 and 14 after irradiation; the changes in the proportion of WBC (neutrophils, lymphocytes and monocytes) on the 7th day after irradiation were analyzed. The 16S rRNA high-throughput sequencing was used to analyze the structure of gut microbiota in mice feces on the 7th day after irradiation, then its correlation with WBC was analyzed. RESULTS The counts of WBC on the 1st, 4th, 7th and 10th day after irradiation, platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in the amifostine group were significantly higher than those in model group (P<0.05). Compared with normal control group,β diversity of gut microbiome showed significant change, relative abundance of Firmicutes increased and that of Bacteroidetes decreased in model group. Amifostine could reverse the change in β diversity of gut microbiome, and the relative abundance of Bacteroidetes and Firmicutes. The model group consisted of four distinct species, namely Allobaculum, Erysipelotrichia, Erysipelotrichales and Erysipelotrichaceae, which were significantly negatively correlated with the proportion of peripheral blood lymphocytes (P<0.01); amifostine group consisted of two distinct species, namely Lactobacillus murinus and L. crispatus, which were significantly negatively correlated with the proportion of neutrophils (P<0.05). CONCLUSIONS Amifostine significantly improves irradiation-induced injury by regulating dysbiosis of LY201816) gut microbiota.
10.The influence of Liuwei Dihuang Wan on the behavior and TLR4/NF-κB signaling pathway of Alzheimer's disease model mice
Yong CUI ; Bing WANG ; Zhongkang ZHU ; Yuan XU ; Yanan GUAN ; Ruihao SI ; Danyu ZHAO ; Xu WANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(2):109-115
Objective:To explore the effects of Liuwei Dihuang Wan on the behaviors and Toll-like receptor 4/nuclear factor kappa-B(TLR4/NF-κB) signal transduction pathway of amyloid β-precursor protein/presenilin-1(APP/PS1) double transgenic mice.Methods:Forty 3-month-old female APP/PS1 mice were randomly divided into model group, low-dose group(0.59 g/kg), medium-dose group(1.18 g/kg), high-dose group(2.36 g/kg)of Liuwei Dihuang Wan(gavaged according to grouped doses), and ibuprofen group(0.04 g/kg, gavage) using a random number table method, with 8 mice in each group.Eight 3-month-old wild-type female C57BL/6 mice with matched body weight were used as the control group.The mice in control group and model group were given an equal volume of 0.9% sodium chloride solution by gavage.The gavage administration was twice a day for a continuous period of 3 months.Morris water maze test was used to detect the learning and memory abilities of mice. ELISA was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β) and immunohistochemistry was used to detect the levels of amyloid β-protein (Aβ), glial fibrillary acidic protein(GFAP) and NF-κB in hippocampal tissue.Western blot was used to detect the expression levels of TLR4, myeloid differentiation primary response gene 88(MyD88), and phosphorylated NF-κB(p-NF-κB) proteins in hippocampal tissue.The SPSS 20.0 software was used for data analysis. Multiple group comparisons were conducted by repeated measure ANOVA or one-way ANOVA.Results:The results of repeated measure ANOVA showed that as for the escape latency of the 6 groups of mice, the interaction effect between time and group was significant ( Finteraction=117.219, P<0.001). The escape latencies of mice in the 6 groups on the 5th day were all lower than those on the 1st day (all P<0.05). The escape latencies of mice in the ibuprofen group and the medium-dose and high-dose groups of Liuwei Dihuang Wan were lower than that in the model group from 1st day to 5th day(all P<0.05). On the 3rd to 5th day, the escape latencies of mice in the medium-dose and high-dose groups of Liuwei Dihuang Wan were lower than those in the low-dose group of Liuwei Dihuang Wan (all P<0.05). There were statistically significant differences in the percentage of residence time in the platform quadrant and the numbers of crossing platform among the 6 groups of mice ( F=5.451, 4.824, both P<0.05). The percentage of residence time in the platform quadrant (50.77±5.49)%, (54.39±5.71)%, (51.98±6.12)%), and the numbers of crossing platform((5.9±1.1) times, (6.0±1.3) times, (5.1±0.8) times) in the high-dose and medium-dose groups of Liuwei Dihuang Wan and the ibuprofen group were all higher than those in the model group ((27.32±3.22)%, (2.2±1.0) times )(all P<0.05). The immunohistochemical results showed that there were statistically significant differences in the integrated optical density values of Aβ, GFAP and NF-κB in the hippocampal tissues of 6 groups of mice ( F=57.52, 45.37, 79.10, all P<0.05). The integrated optical density values of Aβ, GFAP and NF-κB in the high-dose and medium-dose groups of Liuwei Dihuang Wan and the ibuprofen group were all lower than those in the model group (all P<0.05). And the integrated optical density values of Aβ, GFAP, and NF-κB in the high-dose and medium-dose groups of Liuwei Dihuang Wan were all lower than those in the low-dose group of Liuwei Dihuang Wan (all P<0.05). There were statistically significant differences in the levels of serum TNF-α and IL-1β detected by ELISA ( F=3.996, 6.395, both P<0.05) and the proteins levels of TLR4, MyD88, and p-NF-κB in hippocampal tissue detected by Western blot among the 6 groups( F=15.710, 3.522, 4.119, all P<0.05). The serum TNF-α and IL-1β levels in the high-dose and medium-dose groups of Liuwei Dihuang Wan and ibuprofen group were all lower than those in the model group (all P<0.05). The serum TNF-α ((18.90±2.33) ng/L, (21.56±2.49) ng/L) and IL-1β ((5.88±0.80) ng/L, (6.75±0.83) ng/L) levels in the high-dose and medium-dose groups of Liuwei Dihuang Wan were lower than those in the low-dose group ((30.77±2.89) ng/L, (9.11±1.27) ng/L) (all P<0.05). The protein expression levels of TLR4, MyD88, and p-NF-κB in the hippocampus of the high-dose and medium-dose groups of Liuwei Dihuang Wan and ibuprofen group were lower than those of the model group (all P<0.05). The protein expression levels of TLR4 ((0.254±0.091), (0.318±0.122)), MyD88 ((0.229±0.077), (0.386±0.119)), and p-NF-κB ((0.412±0.188), (0.358±0.119)) in the hippocampus of the high-dose and medium-dose groups of Liuwei Dihuang Wan were lower than those of the low-dose group ((0.617±0.172), (0.672±0.166), (0.799±0.227)) (all P<0.05). Conclusion:Liuwei Dihuang Wan can significantly alleviate learning and memory impairment in Alzheimer's disease model mice, possibly by inhibiting TLR4/NF-κB signal pathway, reducing TNF-α and IL-1β expression, thereby alleviate central immune inflammatory response and exert anti Alzheimer's disease effects.


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