1.Huanglian Jiedutang Improves Cognitive Impairment after Schemic Stroke by Regulating Neuron via NF-κB Signaling Pathway
Mengying SUN ; Lizhen WANG ; Tong LI ; Leilei WANG ; Shiyan JIA ; Tingting WANG ; Yanwen YANG ; Kaiqiang SI ; Youxiang CUI ; Zhilong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):68-76
ObjectiveTo investigate the effects of Huanglian Jiedutang (HLJDT) on cognitive function in mice with ischemic stroke (IS) and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB (NF-κB) signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion (MCAO). Sixty C57BL/6J mice were randomly assigned to five groups (n =12 per group), i.e., sham operation, model, HLJDT low-dose (3.9 g·kg-1·d-1), HLJDT high-dose (7.8 g·kg-1·d-1), and Ginkgo biloba extract (GBE, 31.2 mg·kg-1·d-1). Post-operatively, neurological deficit scores (Longa score), cerebral infarct volume assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content were evaluated. Learning and memory were assessed using new object recognition (NOR) and fear conditioning (FC) tests. Hippocampal pathology was examined via hematoxylin and eosin (HE) staining. Immunofluorescence detected expression of glial fibrillary acidic protein (GFAP, astrocyte marker), cellular oncogene Fos (c-Fos, neuronal activation marker), and glutamate decarboxylase 65 (GAD65). Western blot measured nuclear factor-κB inhibitor protein α (IκBα), phosphorylated IκBα (p-IκBα), NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), ionic calcium binding adapter molecule 1 (Iba-1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and apoptosis-related proteins, such as cleaved cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax). Real-time quantitative PCR (Real-time PCR) was used to assess mRNA levels of Iba-1, TNF-α, IL-1β, NF-κB p65, cleaved Caspase-3, Bax, and Bcl-2. ResultsCompared with the sham group, the model group exhibited significantly increased neurological deficit scores, brain water content, and cerebral infarct volume (P<0.01). Hippocampal CA1 neurons were disorganized, showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced (P<0.01). GFAP and c-Fos expression were increased, while GAD65 expression was decreased (P<0.01). Cleaved Caspase-3 and Bax were upregulated, Bcl-2 was downregulated, and the Bax/Bcl-2 ratio was elevated (P<0.01). Expression levels of p-IκBα, p-NF-κB p65, IL-1β, TNF-α, and Iba-1 were significantly increased (P<0.01). Compared with the model group, HLJDT high-dose, low-dose, and GBE groups showed significant improvements in all parameters (P<0.01). Among them, the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests (P<0.01). In this group, GFAP and c-Fos decreased, GAD65 increased (P<0.01), apoptosis-related protein expression was reversed, and NF-κB signaling and related inflammatory factor expression were suppressed (P<0.01). ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS, potentially by inhibiting the NF-κB signaling pathway, thereby reducing neuroinflammation and hippocampal neuronal apoptosis.
2.Action mechanisms and application pathways of biomaterials in promoting corneal alkali burn repair
Hui XIAO ; Dongyan LI ; Jing JI ; Lizhen WANG
Chinese Journal of Tissue Engineering Research 2025;29(10):2162-2170
BACKGROUND:Traditional treatments for corneal alkali burns are limited,especially in controlling inflammation,preventing neovascularization,and inhibiting corneal scarring.Natural,synthetic,or composite materials provide a wide range of treatment options.However,the mechanism by which biomaterials promote corneal alkali burn repair has not yet been systematically understood. OBJECTIVE:To summarize the current research on biomaterials in promoting corneal alkali burn repair in and outside China,and review the mechanism and application of biomaterials in repairing corneal alkali burn. METHODS:The first author searched"cornea,alkali burn,amniotic membrane,hyaluronic acid,collagen,chitosan,polymer materials"as Chinese keywords and"amniotic membrane,hyaluronic acid,collagen,chitosan,polymer,cornea,alkali burn"as English keywords in PubMed,Web of Science,CNKI,and WanFang databases.According to inclusion and exclusion criteria,76 eligible articles were finally included for review. RESULTS AND CONCLUSION:(1)In the field of corneal alkali burn repair,biomaterials such as amniotic membrane,hyaluronic acid,collagen,chitosan,and degradable polymer materials have been widely studied and applied.Each of these biomaterials has its own characteristics,advantages,and disadvantages,and stands out in different aspects.(2)First and foremost,amniotic membranes are considered one of the most promising biomaterials due to their abundance of bioactive factors.They are biocompatible and can regulate the corneal inflammatory response.However,there are issues with donor shortages and susceptibility to infectious diseases.(3)Hyaluronic acid has good moisturizing properties and biocompatibility,and is able to improve the survival rate of corneal cells and increase corneal transparency.(4)The good biocompatibility and scaffold structure of collagen enable the promotion of corneal cell adhesion and proliferation,as well as the reconstruction of corneal tissue structure.(5)Chitosan is recognized for its good biocompatibility and degradability,making it suitable as a carrier for drug delivery and cell transplantation.(6)Degradable polymer materials have good controllability over degradation and can provide a good support and delivery platform for the repair of corneal alkali burns,but further research is needed on their stability and biocompatibility.(7)Overall,there is currently no single biomaterial that can completely address the repair problem of corneal alkali burns,and each biomaterial has its own specific application scenarios and limitations.(8)Future research directions should focus on further improving the properties and structure of biomaterials,exploring more effective combination applications,and deeply understanding the interaction mechanism between biomaterials and corneal tissue,in order to enhance the therapeutic effect of corneal alkali burns and the quality of life of patients.
3.Clinical value of enhanced magnetic resonance imaging-based deep learning model in pre-operative prediction of proliferative hepatocellular carcinoma
Lizhen LIU ; Jie CHENG ; Fengxi CHEN ; Yiman LI ; Yang XU ; Wei CHEN ; Ping CAI ; Qingrui LI ; Xiaoming LI
Chinese Journal of Digestive Surgery 2025;24(7):912-920
Objective:To investigate the clinical value of enhanced magnetic resonance imaging (MRI)-based deep learning model in preoperative prediction of proliferative hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinical data of 906 HCC patients who were admitted to The First Affiliated Hospital of Army Medical University and The Second Affiliated Hospital of Chongqing Medical University from May 2017 to October 2022 were collected. There were 769 males and 137 females, aged (53.2±10.9)years. Of the 906 patients, 815 cases who were admitted to The First Affiliated Hospital of Army Medical University were divided into the training set of 634 patients and the internal validation set of 181 patients using a random number table method with a ratio of 8:2, and 91 patients who were admitted to The Second Affiliated Hospital of Chongqing Medical University were divided into the external validation set. The training set was used to construct the prediction model, while the validation set was used to validate the prediction model. Observation indicators: (1) analysis of factors influencing the pathological classification of HCC patients; (2) deep learning imaging features of HCC patients; (3) evaluation of the efficacy of prediction model for proliferative HCC; (4) validation of the prediction model for proliferative HCC; (5) prognosis of HCC patients. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Multivariate analysis was conducted using the binary Logistic regression model. The model perfor-mance was evaluated through five-fold cross-validation, and receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of the model based on the area under curve (AUC), sensitivity, and specificity. The Delong test was used to compare the diagnostic performance of models. The Hosmer-Lemeshow test was employed to evaluate the calibration of models. The optimal cutoff value of the prediction model was determined by the maximum Youden index, with the value >0.175 indicating high-risk patients and value ≤0.175 indicating low-risk patients.The Kaplan-Meier method was used to calculate the survival rate and the Log-rank test was used for survival analysis. Results:(1) Analysis of factors influencing the pathological classification of HCC patients. Of 634 patients in the training set, there were 190 cases of proliferative HCC and 444 cases of non-proliferative HCC. Results of multivariate analysis showed that alpha fetoprotein (AFP) ≥400 μg/L and tumor diameter >5 cm were independent risk factors for pathological type of HCC as proli-ferative [ odds ratio=1.73, 1.88, 95% confidence interval ( CI) as 1.19-2.50, 1.30-2.71, P<0.05]. (2) Deep learning imaging features of HCC patients. In the training set of 634 patients, the probability predicted by MRI-based deep learning model was 84.8%(30.5%,95.4%) for proliferative HCC and 5.8%(3.2%,12.5%) for non-proliferative HCC, showing a significant difference between them ( Z=-16.01, P<0.05). (3) Evaluation of the efficacy of prediction model for proliferative HCC. In the training set, the AUC of clinical prediction model for proliferative HCC was 0.63(95% CI as 0.59-0.68, P<0.05), with sensitivity of 54.74% and specificity of 64.19%. The AUC of MRI-based deep learning prediction model was 0.90(95% CI as 0.87-0.93, P<0.05), with sensitivity of 80.53% and specificity of 86.94%. The AUC of combined MRI-based deep learning with clinical prediction model was 0.90 (95% CI as 0.87-0.93, P<0.05), with sensitivity of 83.16% and specificity of 86.04%. Results of Delong test showed that there was a significant difference between the combined MRI-based deep learning with clinical prediction model and the clinical prediction model ( P<0.05), and there was no signifi-cant difference between the combined MRI-based deep learning with clinical prediction model and the MRI-based deep learning prediction model ( P>0.05). Results of Hosmer-Lemeshow test showed good calibration for the clinical prediction model, the MRI-based deep learning prediction model and the combined MRI-based deep learning with clinical prediction model ( χ2=0.84, 6.38, 3.93, P>0.05), indicating that the predicted probabilities of these three prediction models matched the actual risk well. (4) Validation of the prediction model for proliferative HCC. Results of validation of the prediction model in internal validation set showed the AUC of MRI-based deep learning prediction model for proliferative HCC was 0.84(95% CI as 0.77-0.91, P<0.05), with sensitivity of 82.35% and specificity of 77.69%. Results of validation of the prediction model in external validation set showed the AUC of MRI-based deep learning prediction model for proliferative HCC was 0.81(95% CI as 0.71-0.92, P<0.05), with sensitivity of 70.00% and specificity of 81.69%. (5) Prognosis of HCC patients. Of the 906 patients, the 1-, 3-, and 5-year recurrence-free survival rates for 645 proliferative HCC patients were 56.9%, 31.4%, and 29.1%, respectively, and the 1-, 3-, and 5-year recurrence-free survival rates for 261 non-proliferative HCC patients were 88.8%, 68.6%, and 56.0%, respectively. There were significant differences in recurrence-free survival time between proliferative HCC and non-proliferative HCC patients of the training set, internal validation set and external validation set ( P<0.05). The 1-, 3-, 5-year recurrence-free survival rates for 331 high-risk HCC patients were 64.6%, 50.4%, 43.6%, versus 88.5%, 71.9%, 62.7% for 575 low-risk HCC patients. There were significant differences in recurrence-free survival time between high-risk HCC patients and low-risk HCC patients of the training set, internal validation set and external validation set ( P<0.05). Conclusion:The MRI-based deep learning model can effectively predict proliferative HCC and recurrence-free survival of patients before the surgery.
4.Research on the Factors Influencing the Evolution of COPD Qi Deficiency Syndrome Based on Nonlinear Mixed Effects Model
Weike LI ; Mingyang YI ; Yuanyuan NI ; Lizhen YAN ; Jianxin GUAN ; Shihao WANG ; Huijie WANG ; Jiansheng LI ; Zhiwan WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(8):2205-2214
Objective To provide methodological examples for related research,the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease(COPD)based on a nonlinear mixed effects model was explored.Methods A research questionnaire on the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease was developed,and clinical data of 650 COPD patients on the 1st and 14th day of acute exacerbation,the 1st and 28th day of risk window,the first day of stable period,and the 90th day were dynamically collected from 10 tertiary hospitals across the country.8 baseline data including gender and age were collected through the PROC NLMIXED process by SAS 9.4 software.Coronary heart disease,diabetes and hypertension accounted for the highest proportion.Nine concurrent syndromes including wind cold syndrome and phlegm heat syndrome were used as fixed effects,and individual level was used as random effects to gradually fit the model and screen the influencing factors of Qi deficiency syndrome in the entire process of disease occurrence and development.Results A total of 637 eligible cases were included,and clinical datas were dynamically collected on the 1st and 14th day of acute exacerbation,the 1st and 28th day of the risk window,the 1st and 90th day of the stable period.It was found that the number of acute exacerbations,alcohol consumption,concomitant hypertension,coronary heart disease,blood stasis syndrome,yin deficiency syndrome,yang deficiency syndrome,6-minute walking distance,and the modified Medical Research Council Dyspnea Questionnaire(mMRC)had an impact on the evolution of Qi deficiency syndrome in the previous year(P<0.05).Conclusion The use of a nonlinear mixed effects model revealed the relevant factors affecting the evolution of Qi deficiency syndrome from complex multi temporal dynamic data,providing methodological references for other related studies.
5.Analysis of the effectiveness of technology transfer of research-oriented hospital:a case study of an af-filiated hospital of a university in Guangdong province
Yi WEI ; Shiying CHEN ; Lizhen LI ; Cuiwei CHEN ; Guiping LIN ; Xiuying CUI
Modern Hospital 2025;25(1):143-147
Objective This study aims to explore effective approaches for the transfer of medical scientific and techno-logical achievements to promote the development of research-oriented hospitals.Methods The technology transfer achievements of an affiliated hospital of a university in Guangdong Province over the past six years(2018-2023)were statistically analyzed.The challenges faced during the transfer process,the measures taken,and the current achievements were discussed.Results The number of patent authorizations and authorized departments in the hospital has increased year by year.The transfer rate has risen from 0%in 2019 to 6.69%in 2023.Currently,46 projects have been successfully transferred,with a total transfer amount exceeding 30 million yuan,indicating significant effectiveness in the transfer of medical scientific and technological achievements.Conclusion The hospital attaches great importance to and overall manages the transfer process,establishing a sound manage-ment structure,improving incentive and support systems,and regularly conducting special lectures,training,and guidance.These efforts guide researchers to start from clinical problems and ultimately serve clinical diagnosis and treatment,creating a fa-vorable environment for technology transfer,improving the transfer rate,and promoting the development of research-oriented hos-pitals.
6.The relationship between the serum levels of vascular endothelial growth factor, matrix metalloproteinase-9, S100 calcium binding protein with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes
Lizhen CHEN ; Lihua CHANG ; Fei LI ; Fenxia LI ; Yanli ZHENG ; Rongrong XU
Chinese Journal of Postgraduates of Medicine 2025;48(7):608-614
Objective:To investigate the relationship between the serum levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), S100 calcium binding protein B (S100B) with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes.Methods:The clinical data of 153 pregnant women with gestational diabetes (research group) and 153 healthy pregnant women (control group) in the Second Affiliated Hospital of Xi ′an Medical University from January 2020 to October 2023 were retrospectively analyzed. The serum levels of VEGF, MMP-9 and S100B were measured by enzyme linked immunosorbent assay, and the fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin and glycated hemoglobin were measured, and the homeostasis model assessment insulin resistance index (HOMA-IR) was calculated. The adverse outcomes of pregnant women with gestational diabetes were recorded. Pearson method was used to analyze the correlation between glycolipid metabolism indexes and VEGF, MMP-9, S100B in pregnant women with gestational diabetes. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcome in pregnant women with gestational diabetes. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of VEGF, MMP-9 and S100B on adverse pregnancy outcome in pregnant women with gestational diabetes. Results:The fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol, LDL-C, VEGF, MMP-9 and S100B in research group were significantly higher than those in control group: (9.42 ± 0.65) mmol/L vs. (4.13 ± 0.46) mmol/L, (16.58 ± 2.37) mU/L vs. (13.41 ± 2.05) mU/L, (7.28 ± 0.46)% vs. (4.35 ± 0.39)%, 4.83 ± 0.42 vs. 2.71 ± 0.37, (3.41 ± 0.67) mmol/L vs. (2.85 ± 0.63) mmol/L, (5.54 ± 1.56) mmol/L vs. (5.12 ± 1.50) mmol/L, (3.14 ± 0.97) mmol/L vs. (2.86 ± 0.93) mmol/L, (184.02 ± 30.25) ng/L vs. (156.33 ± 26.41) ng/L, (45.78 ± 7.56) μg/L vs. (29.36 ± 5.03) μg/L and (117.51 ± 25.12) ng/L vs. (89.74 ± 22.46) ng/L, the HDL-C was significantly lower than that in control group: (1.34 ± 0.27) mmol/L vs. (1.42 ± 0.30) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Pearson correlation analysis result showed that VEGF, MMP-9, S100B in pregnant women with gestational diabetes were positively correlated with fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol and LDL-C ( P<0.01), negatively correlated with HDL-C ( P<0.01). Among 153 pregnant women with gestational diabetes, 49 had adverse pregnancy outcome, and 104 had good pregnancy outcome. The VEGF, MMP-9 and S100B in pregnant women with adverse pregnancy outcome were significantly higher than those in pregnant women with good pregnancy outcome: (212.75 ± 28.63) ng/L vs. (170.49 ± 26.58) ng/L, (52.37 ± 7.14) μg/L vs. (42.68 ± 6.35) μg/L and (136.83 ± 23.62) ng/L vs. (108.41 ± 21.35) ng/L, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that VEGF, MMP-9 and S100B were independent risk factors for adverse pregnancy outcome in pregnant women with gestational diabetes ( OR = 7.013, 5.382 and 6.129; 95% CI 5.206 to 9.447, 3.449 to 8.398 and 3.520 to 10.673; P<0.01). ROC curve analysis result showed that the area under the curve of VEGF, MMP-9 combined S100B in predicting adverse pregnancy outcome in pregnant women with gestational diabetes was significantly larger than that of VEGF, MMP-9 and S100B alone (0.945 vs. 0.863, 0.847 and 0.801; P<0.05 or <0.01), with sensitivity of 89.80% and specificity of 91.30%. Conclusions:The high serum levels of VEGF, MMP-9 and S100B are associated with abnormal glycolipid metabolism and adverse pregnancy outcome in pregnant women with gestational diabetes, and the combination of the three indexes has a high predictive value for adverse pregnancy outcome.
7.Analysis of the effectiveness of technology transfer of research-oriented hospital:a case study of an af-filiated hospital of a university in Guangdong province
Yi WEI ; Shiying CHEN ; Lizhen LI ; Cuiwei CHEN ; Guiping LIN ; Xiuying CUI
Modern Hospital 2025;25(1):143-147
Objective This study aims to explore effective approaches for the transfer of medical scientific and techno-logical achievements to promote the development of research-oriented hospitals.Methods The technology transfer achievements of an affiliated hospital of a university in Guangdong Province over the past six years(2018-2023)were statistically analyzed.The challenges faced during the transfer process,the measures taken,and the current achievements were discussed.Results The number of patent authorizations and authorized departments in the hospital has increased year by year.The transfer rate has risen from 0%in 2019 to 6.69%in 2023.Currently,46 projects have been successfully transferred,with a total transfer amount exceeding 30 million yuan,indicating significant effectiveness in the transfer of medical scientific and technological achievements.Conclusion The hospital attaches great importance to and overall manages the transfer process,establishing a sound manage-ment structure,improving incentive and support systems,and regularly conducting special lectures,training,and guidance.These efforts guide researchers to start from clinical problems and ultimately serve clinical diagnosis and treatment,creating a fa-vorable environment for technology transfer,improving the transfer rate,and promoting the development of research-oriented hos-pitals.
8.Characteristics of cardiopulmonary exercise testing and analysis of risk factors for decreased aerobic capacity in children with non-acute bronchial asthma exacerbations
Pengli WANG ; Lizhen HUANG ; Wujun JIANG ; Wenjing GU ; Lina XU ; Pengyun LI ; Xuena XU ; Qianying YU ; Xiaoyan SHI ; Chuangli HAO
Chinese Journal of Applied Clinical Pediatrics 2025;40(8):595-602
Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.
9.Research on the Factors Influencing the Evolution of COPD Qi Deficiency Syndrome Based on Nonlinear Mixed Effects Model
Weike LI ; Mingyang YI ; Yuanyuan NI ; Lizhen YAN ; Jianxin GUAN ; Shihao WANG ; Huijie WANG ; Jiansheng LI ; Zhiwan WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(8):2205-2214
Objective To provide methodological examples for related research,the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease(COPD)based on a nonlinear mixed effects model was explored.Methods A research questionnaire on the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease was developed,and clinical data of 650 COPD patients on the 1st and 14th day of acute exacerbation,the 1st and 28th day of risk window,the first day of stable period,and the 90th day were dynamically collected from 10 tertiary hospitals across the country.8 baseline data including gender and age were collected through the PROC NLMIXED process by SAS 9.4 software.Coronary heart disease,diabetes and hypertension accounted for the highest proportion.Nine concurrent syndromes including wind cold syndrome and phlegm heat syndrome were used as fixed effects,and individual level was used as random effects to gradually fit the model and screen the influencing factors of Qi deficiency syndrome in the entire process of disease occurrence and development.Results A total of 637 eligible cases were included,and clinical datas were dynamically collected on the 1st and 14th day of acute exacerbation,the 1st and 28th day of the risk window,the 1st and 90th day of the stable period.It was found that the number of acute exacerbations,alcohol consumption,concomitant hypertension,coronary heart disease,blood stasis syndrome,yin deficiency syndrome,yang deficiency syndrome,6-minute walking distance,and the modified Medical Research Council Dyspnea Questionnaire(mMRC)had an impact on the evolution of Qi deficiency syndrome in the previous year(P<0.05).Conclusion The use of a nonlinear mixed effects model revealed the relevant factors affecting the evolution of Qi deficiency syndrome from complex multi temporal dynamic data,providing methodological references for other related studies.
10.Study on Graded Quantitative Diagnosis of Lung Qi Deficiency Syndrome in Chronic Obstructive Pulmonary Disease Based on Latent Class Analysis Combined with Hidden Structure Model
Weike LI ; Mingyang YI ; Yuanyuan NI ; Lizhen YAN ; Jianxin GUAN ; Shihao WANG ; Huijie WANG ; Zhiwan WANG
Journal of Traditional Chinese Medicine 2025;66(7):710-716
ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease (COPD) based on latent class analysis combined with a hidden structure model. MethodsClinical data, including the four diagnostic methods of traditional Chinese medicine (TCM), were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software, and each patient was classified into one of three severity categories (mild, moderate, or severe) based on probabilistic parameterization, parameter estimation, and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this, Lantern 5.0 software was used to construct hidden structure models for mild, moderate, and severe lung qi deficiency syndrome, and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity, the optimal model was determined when the number of latent classes was three, categorizing lung qi deficiency syndrome into mild (298 cases), moderate (164 cases), and severe (283 cases). Hidden structure models were separately developed for each severity level, and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights (P>0.05), leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed: shortness of breath (diagnostic value 9.3, diagnostic weight 86.92%), dyspnea on exertion (8.2, 76.64%), low voice and reluctance to speak (6.7, 62.62%), poor appetite (4.0, 37.38%), loose stools (4.0, 37.38%), weak cough sound (2.9, 27.10%), wheezing (2.3, 21.50%), fatigue (1.8, 16.82%), spontaneous sweating (1.7, 15.89%), susceptibility to colds (1.6, 14.95%), swollen tongue (1.4, 13.08%), teeth marks on the tongue edge (1.2, 11.21%), deep pulse (1.6, 14.95%), with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed: weak cough sound (15.1, 61.13%), soreness and weakness of the waist and knees (12.6, 51.01%), shortness of breath (11.1, 44.94%), low voice and reluctance to speak (8.3, 33.60%), frequent nocturia (6.1, 24.70%), spontaneous sweating (3.7, 14.98%), susceptibility to colds (3.5, 14.17%), teeth marks on the tongue edge (7.8, 31.58%), pale tongue body (1.9, 7.69%), white tongue coating (5.5, 22.27%), thin pulse (1.5, 6.07%), with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome, providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

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