1.23-Hydroxybetulinic Acid Inhibits NNK and LPS-induced Lung Inflammation-related Carcinogenesis by Regulating Immune Cells in Mice
Penghaobang LIU ; Wenbin DUAN ; Yajuan CHEN ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):98-106
ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid (23-HBA), a key constituent of Pulsatillae Radix, on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and lipopolysaccharide (LPS) in mice, alongside exploring its influence on immune cells and delving into the underlying mechanisms. MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control, model, aspirin (10 mg·kg-1), and low-, medium-, and high-dose (3.75, 7.5, 15 mg·kg-1, respectively) 23-HBA groups. The treatment lasted for 26 weeks, after which the spleen, lung, and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 (TTF-1), neuron-specific enolase (NSE), and proliferating cell nuclear antigen (Ki-67) in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages, myeloid-derived suppressor cells (MDSCs), and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 (JAK2), Src homology 2 domain-containing phosphatase 2 (SHP2), and suppressor of cytokine signaling 3 (SOCS3). Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), p53, and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA. ResultsCompared with the normal group, the lung and spleen indexes of the model group were increased to varying degrees (P<0.05, P<0.01), the expression of TTF-1, NSE and Ki-67 protein was significantly increased (P<0.05, P<0.01), and the serum levels of TNF-α, IL-1β and IL-6 were significantly increased (P<0.01). The number of macrophages in the model group was significantly decreased (P<0.01), and the number of exhausted T cells and MDSCs was significantly increased (P<0.05, P<0.01). Compared with the model group, the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly (P<0.05), and the lung index of mice in the middle dose group of 23-HBA decreased significantly (P<0.05). The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased (P<0.05), and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased (P<0.05, P<0.01). The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased (P<0.05), and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased (P<0.05, P<0.01). In addition, 23-HBA had strong molecular docking ability to SHP2, SOCS3 and JAK2 (≥7 kcal·mol-1), and significantly down-regulated the protein levels of p-STAT3, SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma (P<0.01). Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses, improving the tumor immune microenvironment, and regulating key signaling pathways.
2.Identification of Dalbergia odorifera and Its Counterfeits by HS-GC-MS
Li ZHAO ; Xiaowei MENG ; Jiarong LI ; Qing ZHU ; Xianwen WEI ; Ronghua LIU ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):156-163
ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits, in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the GC conditions were heated by procedure(the initial temperature of the column was 50 ℃, the retention time was 1 min, and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min), the carrier gas was helium, and the flow rate was 1.0 mL·min-1, the split ratio was 10∶1, and the injection volume was 1 mL. The MS conditions used electron bombardment ionization(EI) with the scanning range of m/z 35-550. The compound species were identified by database matching, the relative content of each component was calculated by the peak area normalization method, and principal component analysis(PCA), orthogonal partial least squares-discrimination analysis(OPLS-DA) and cluster analysis were performed on the detection results by SIMCA 14.1 software, and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection(VIP) value>2 and P<0.05. ResultA total of 26, 17, 8, 22, 24 and 7 volatile components were identified from D. odorifera, D. bariensis, D. latifolia, D. benthamii, D. pinnata and D. cochinchinensis, respectively. Among them, there were 11 unique volatile components of D. odorifera, 6 unique volatile components of D. bariensis, 3 unique volatile components of D. latifolia, 6 unique volatile components of D. benthamii, 8 unique volatile components of D. pinnata, 4 unique volatile components of D. cochinchinensis. The PCA results showed that, except for D. latifolia and D. cochinchinensis, which could not be clearly distinguished, D. odorifera and other counterfeits could be distributed in a certain area, respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each, indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally, a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits, which is suitable for rapid identification of them.
3.Construction of a therapeutic effect prediction model for bronchial asthma
Qidong HUANG ; Minxi LI ; Yilong LI ; Wanqi SHAO ; Shumei ZHAO ; Xiaoyan GONG ; Lindu ZHAO ; Lanying LIU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):729-740
Objective We aimed to investigate the feasibility and method of constructing a traditional Chinese medicine(TCM)curative effect prediction model based on the data of Kechuanting acupoint plastering therapy in the treatment of bronchial asthma(asthma).Methods Data from the Chronic Disease Management Research Platform of 303 patients with asthma who were treated with Kechuanting acupoint plastering therapy for 6 weeks in the Department of Acupuncture and Rehabilitation of Jiangsu Hospital of Traditional Chinese Medicine from June to August 2018 to 2021 were selected.We used Phyton 3.10 for statistical analysis.After data preprocessing,the influencing factors were used to build models by Logistic regression,support vector machine,K-means clustering algorithm,Bayes algorithm,random forest method and Light gradient boosting machine(LightGBM)respectively,with the improvement of asthma control test score(ACT),forced expiratory volume in one second(FEV1)and exhaled nitric oxide(FeNO)as the outcome indicators.Then,the models were compared and analyzed.Subsequently,the superior model was used to establish the efficacy prediction model and verify its stability to obtain the accuracy rate and eliminate the relatively important factors.Results The accuracy rate of the Kechuanting acupoint plastering therapy curative effect prediction model established by the LightGBM model was more than 70%.Five important factors were selected,including allergic history,tabacco and alcohol abuse,plastering duration,ACT before treatment,and FeNO before treatment.According to the classification analysis and the relationship between the important factors and the outcome indicators,Kechuanting acupoint plastering therapy significantly improved the ACT of patients with no history of allergy,no tabacco and alcohol abuse,and poor ACT:5-15 points(P<0.05).Furthermore,Kechuanting acupoint plastering therapy improved FeNO more significantly in patients with more than 3 years of treatment than those with no more than 3 years(P<0.05).However,Kechuanting acupoint plastering therapy only improved FeNO in a few patients with poor asthma control levels(P<0.05)and severe airway inflammation(FeNO>50×10-9)(P>0.05).Conclusion Acupoint plastering application has a significant effect on improving the control level of asthma,but its effect on improving airway inflammation is limited.It is feasible to use data from the chronic disease management research platform to construct the prediction model.After optimization and testing,the predictive model established based on the data of this study may provide an effective evaluation tool for targeted clinical treatment.
4.Thoughts on the Formulation of"2023 Guidelines for Diagnosis and Treatment of Depression with Integrative Chinese and Western Medicine"
Liyuan GUO ; Jianjun WANG ; Zhen WANG ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):12-18
The integration of Chinese and Western Medicine(ICWM)in the diagnosis and treatment of depression has been a long-standing issue in the field of mental health.In order to maximize the benefits of this combined approach,the"2023 Guidelines for Diagnosis and Treatment of Depression with Integrative Chinese and Western Medicine"(GDTD-ICWM)has been developed based on organizing evidence-based and standardized workflows for ICWM.This article aims to discuss the background,highlights,summary and outlook of the"Guidelines",as well as offer operational suggestions to guide clinical practices in order to strengthen the implementation,practice and promotion of the"Guidelines".
5.Comparative Study on the Topological Attributes of Deficiency and Excess Pattern of Cerebral Small Vessel Disease Mild Cognitive Impairment Based on fMRI Graph Theory Network
Jianjun WANG ; Weimin YANG ; Haotao ZHENG ; Jianxiang CHEN ; Dongbin CAI ; Hanqing LYU ; Xiude QIN ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):69-75
Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.
6.Efficacy and Safety of Acupuncture in Treating Major Depressive Disorders:A Systematic Review and Meta Analysis
Wangtao LI ; Mingqi TU ; Liyuan GUO ; Yiyin HU ; Haomin SUN ; Peiqi LI ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):76-87
Objective To evaluate the effectiveness and safety of acupuncture in patients with Major Depressive Disorders.Methods Search the database for relevant literature published before April 15,2023.Select randomized controlled trial that meeting the enrollment criteria,evaluate the quality of the literature and classify before meta-analysis systematic evaluation.Results 15 RCTs are included in this study,with a total of 1077 patients.The results showed that acupuncture treatment,compared with antidepressants alone,The score of Hamilton Depression Scale(HAMD)in patients with liver-qi depression disorder[MD=-0.73,95%CI(-1.22,-0.24),P<0.05],the score of TCM Syndrome Scale[MD=-1.89,95%CI(-2.35,-1.44),P<0.001],effective rate[RR=1.09,95%CI(1.03,1.153),P=0.001]and TESS score[MD=-2.76,95%CI(-3.68,-1.85),P<0.001]were statistically significant.Compared with fluoxetine hydrochloride,the effective rate of HAMD scale score was statistically significant[RR=1.07,95%CI(1.01,1.14),P<0.05].Conclusion Compared with antidepressants alone,acupuncture therapy has the advantages for the improvement of HAMD score in patients,the improvement of Traditional Chinese medicine symptoms,and significantly less adverse effects than those in the control group.Through this study,it is considered that acupuncture can be a safe and effective treatment modality.However,due to the quantity and quality of the included literature,the above conclusions still need to be verified by more high-quality clinical trials.
7.Circadian Rhythm of Blood Pressure in Patients with Masked Hypertension and its Relationship with Twelve Two-hour Periods: A Cross-sectional Study
Lingli WANG ; Ming LIU ; Mingchun WANG ; Shumei ZHAO ; Xiaoyan GONG ; Mengyu FU ; Xiao YUAN ; Lanying LIU
Journal of Traditional Chinese Medicine 2024;65(14):1469-1477
ObjectiveTo explore the characteristics of circadian rhythm of blood pressure in patients with masked hypertension (MH) and its relationship with twelve two-hour peirods, providing a basis for early detection and intervention of MH. MethodsPatients who underwent 24-hour ambulatory blood pressure examination in the ambulatory blood pressure room of Jiangsu Province Hospital of Chinese Medicine from January to December 2022 were enrolled, and according to their outpatient blood pressure measurements, 24-hour ambulatory blood pressure monitoring and follow-up survey results, the MH, essential hypertension (EH) and normal blood pressure groups were classified, with 50 cases in each group. The general data, office blood pressure and 24-hour ambulatory blood pressure monitoring data were collected. The circadian rhythm of blood pressure including 24-hour average systolic blood pressure (24h SBP), daytime average systolic blood pressure (d SBP), nighttime average systolic blood pressure (n SBP), 24-hour average diastolic blood pressure (24h DBP), daytime average diastolic blood pressure (d DBP), and nighttime average diastolic blood pressure (n DBP) were compared among the groups, and the nighttime blood pressure dipping percentage was calculated. The type of circadian rhythm was determined based on the nighttime blood pressure dipping percentage. The variability of blood pressure including 24h SBP standard deviation (24h SBP-SD), d SBP standard deviation (dSBP-SD), n SBP standard deviation (nSBP-SD), 24h DBP standard deviation (24h DBP-SD), d DBP standard deviation (dDBP-SD), and n DBP standard deviation (nDBP-SD) were compared among groups, and the corresponding coefficient of variation (CV), that is, 24h SBP-CV, d SBP-CV, n SBP-CV, 24h DBP-CV, d DBP-CV and n DBP-CV, were calculated. Based on the 24-hour ambulatory blood pressure monitoring results, the twelve two-hour average SBP and DBP in each group were calculated and compared. Simultaneously, patients with EH were divided into grades 1, 2, and 3 for further stratified analysis. ResultsThe age of the MH group was significantly higher than that of the EH group and the normal blood pressure group (P<0.01). The body mass index (BMI) and the proportion of smoking and alcohol consumption in the MH group and the EH group were significantly higher than those in the normal blood pressure group (P<0.05 or P<0.01). In the normal blood pressure group, there were 49 dipper patterns (98.0%) and one non-dipper pattern (2.0%); in the MH group, there were two dipper patterns (4.0%), 29 non-dipper patterns (58.0%) and 19 reverse-dipper patterns (38.0%); in the EH group, there were 20 dipper patterns (40.0%), 23 non-dipper patterns (46.0%) and seven reverse-dipper patterns (14.0%). Compared to the normal blood pressure group, the groups of MH and EH had significantly decreased proportion of dipper pattern and increased proportion of non-dipper and reverse-dipper pattern (P<0.01); the proportion of dipper pattern in the MH group was lower than that in the EH group, while the proportion of reverse-dipper pattern was higher (P<0.01). Compared to those in the normal blood pressure group, n SBP and n DBP in the MH group, as well as the the average SBP and average DBP at Zi hour (子时, 23:00-1:00), Chou hour (丑时, 1:00-3:00), Yin hour (寅时, 3:00-5:00), Mao hour (卯时, 5:00-7:00) and average SBP at Hai hour (亥时, 21:00-23:00) in the MH group increased,while the average DBP at Si hour (巳时, 9:00-11:00) decreased (P<0.01); 24h SBP, 24h DBP, d SBP, d DBP, n SBP, and n DBP,d SBP-SD, n SBP-SD,n DBP-SD increased, as well as the average SBP and average DBP at twelve two-hour periods increased in the EH group,while the 24h SBP-CV, 24h DBP-CV,and d DBP-CV in the EH group decreased(P<0.05 or P<0.01). The EH group had higher 24h SBP, 24h DBP, d SBP, d DBP, n SBP, n DBP, 24h DBP-SD and n DBP-SD , as well as higher average SBP and DBP at all twelve two-hour periods, and lower d DBP-CV than the MH group(P<0.05 or P<0.01). The EH group had 18 cases of grade 1 (36.0%), 19 cases of grade 2 (38.0%) and 13 cases of grade 3 (26.0%), with no significant differences among groups (P>0.05). ConclusionThe circadian rhythm of blood pressure in MH patients are mostly non-dipper and reverse-dipper patterns, and the abnormal elevation of blood pressure is obvious at Zi hour, Chou hour, Yin hour and Mao hour (23:00-7:00).
8.Effect of Jogging on Efficacy in Patients with Depressive Disorder with Liver Depression and Spleen Deficiency
Yiying HU ; Wei LI ; Hui ZHANG ; Liyuan LUO ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1440-1445
Objective To explore the effect of jogging on the patients with depression disorder of liver-stagnation and spleen-deficiency.Methods 100 patients with liver-stagnation and spleen-deficiency depression disorder were randomly selected from Tongde Hospital of Zhejiang Province from March to September 2022.They were divided into observation group and control group(50 cases each)by random number table method.The control group received conventional antidepressant drug treatment,and the observation group was given jogging exercise regimen on the basis of the control group:exercise at least 4 times a week,30-60 min each time,and the heart rate was maintained at 110-120 times/min for 4 weeks.The depressive disorder of the patients was assessed by Zung's Self-rating Depression Scale(SDS)and 17-item Hamilton Depression Scale(HAMD-17).Results After jogging exercise intervention,the total effective rate of the observation group was 94%,which was significantly higher than that of the control group 80%(P<0.05).HAMD-17 score was significantly lower in the observation group than in the control group after intervention(F=12.575,P<0.05).The scores of cognitive impairment,block and sleep disturbance in the observation group were significantly lower than those in the control group after intervention(F=12.575,P<0.05).The body weight factor scores of the observation group and the control group were significantly higher after intervention than before intervention(P>0.05).Conclusions Jogging exercise intervention therapy can significantly improve the depression of patients with liver-qi and spleen-deficiency depression disorder,and jogging can be an effective method to prevent and treat depression disorder.
9.Distribution and significance of CD1a+and CD83+dendritic cells in lung tissue of COPD mice
Lanying ZHANG ; Fuan ZHANG ; Maomao LIU ; Jie CHEN ; Jian ZHOU ; Yuting LIU ; Yao OUYANG
Tianjin Medical Journal 2024;52(9):913-916
Objective To study the distribution and significance of CD1a and CD83 positive dendritic cells(DCs)in lung tissue of chronic obstructive pulmonary disease(COPD)mice.Methods Twenty C57BL/6 mice were randomly divided into the air control group and the smoked COPD group(n=10 for each group).COPD mouse model was established using cigarette smoking method.Mice were executed within 24 h after the last cigarette smoking,and right lower lung was collected.Body mass changes and lung histopathological changes of mice were observed in two groups.Mean linear intercept(MLI)was measured,and expression levels of CD1a+and CD83+DCs in lung tissue were detected by immunohistochemistry.Results The body mass of mice at 7,14,21 and 28 d after modeling was lower in the smoked COPD group than that in the air control group(P<0.05).HE staining showed that the normal alveolar structure of lung tissue of mice in the smoked group was disrupted,with multiple alveoli fused with each other to form a larger alveolar lumen,a large number of inflammatory cells infiltrated in alveolar intervals,and walls of the alveoli were thickened.COPD modeling was successful.Compared with the air control group,MLI values(μm)increased in the smoked COPD group(28.30±3.47 vs.50.40±3.60),and the number of CD1a+DCs(per field of view)in lung tissue increased(9.58±2.18 vs.17.08±3.67),while the number of CD83+DCs(per field of view)decreased(19.78±4.95 vs.8.02±3.30)(all P<0.05).Conclusion The number of CD1a+DCs in lung tissue is increased and the number of CD83+DCs in lung tissue is decreased in the smoked COPD group of mice,and cigarette smoking may have impaired DC maturation.
10.Effect of Euphorbia helioscopia Aqueous Extract on Chronic Obstructive Pulmonary Disease and Precancerous Lesion-associated Proteins of Lung Tissues in Mice Induced by Cigarette Smoke
Ziye ZHOU ; Huimiao MA ; Lanying CHEN ; Wenbin DUAN ; Lihua LIN ; Peng LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):84-94
ObjectiveTo investigate the protective effect and mechanism of Euphorbia helioscopia aqueous extract (EHE) on mice with chronic obstructive pulmonary disease (COPD) and its influence on precancerous lesion-associated proteins in lung tissues induced by cigarette smoke (CS). MethodThe COPD model was induced by CS in 60 mice and the model mice were randomly divided into control group, model group, positive drug group (dexamethasone, 2 mg·kg-1), and low-, medium-, and high-dose EHE groups (1.875, 3.75, 7.5 g·kg-1). The high-performance liquid chromatography (HPLC) method was used to determine the related components in EHE. The changes in end-expiratory pause (EEP), airway resistance (Penh), expiratory flow at 50% vital capacity (EF50), and other pulmonary function indexes were detected by the spirometer. The levels of inflammatory factors, such as interleukin (IL)-2, IL-5, IL-18, IL-17A, and IL-27 in bronchoalveolar lavage fluid (BALF) of mice were detected by high-throughput liquid protein chip technology. Hematoxylin-eosin (HE) staining was used to detect the pathological changes in lung tissues in mice. The content of malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione peroxidase (GSH-Px) in lung tissues was determined by the colorimetric method. The mRNA relative expression of tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-12 (MMP-12) was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Immunohistochemistry (IHC) was used to detect the expression of tumor protein (P53) and cell proliferation-associated antigen (Ki67) in lung tissues, and Western blot was used to detect the relative expression of tumor suppressor protein (P16), DNA (cytosine-5)-methyltransferase 1 (DNMT1), and fragile histidine triad (FHIT) in lung tissues. ResultThe results showed that the main compounds in EHE included phenols (gallic acid and protocatechuic acid) and flavonoids (such as hyperoside, rutin, myricetin, naringenin, quercetin, luteolin, kaempferol, and licorice chalcone A), among which gallic acid and rutin were the highest in content. Compared with normal group, model group showed increased levels of EEP, EF50, and Penh (P<0.05), and showed increased MDA and MPO levels (P<0.01) and decreased GSH-Px (P<0.01), and the model group displayed increased levels of IL-2, IL-5, IL-18, IL-17A, IL-27, TNF-α, TGF-β, MMP-2, MMP-9, and MMP-12 (P<0.05). And the model group exhibited up-regulated expression of P53, Ki67, and FHIT in lung tissues (P<0.01) and down-regulated expression of DNMT1 and P16 (P<0.01). Compared with model group, the EHE groups showed decreased EEP and EF50 levels (P<0.05). The pathological injury of lung tissues in mice of the model group was observed under HE staining, and the pathological injury of basal cell hyperplasia of lung tissues was gradually improved after treatment with EHE. The EHE groups showed reduced levels of MDA and MPO (P<0.01) and increased GSH-Px (P<0.01). The EHE groups displayed decreased levels of IL-2, IL-5, IL-18, IL-17A, IL-27, TNF-α, TGF-β, MMP-2, MMP-9, and MMP-12 (P<0.05). And the EHE groups showed down-regulated Ki67 and FHIT in lung tissues (P<0.05) and up-regulated expression of P53 and DNMT1 (P<0.05). ConclusionEHE can protect mice from COPD and inhibit precancerous lesions, and the mechanism may be related to the inhibition of inflammation and oxidative stress response, regulation of protease and antiprotease imbalance, and regulation of epithelial cell growth.

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