1.Research on the mechanism of RNA m 6A modification in age-related idiopathic pulmonary fibrosis
Li QIAN ; Ziyue SUN ; Yongkang HAN ; Yufeng DU ; Xiaohui WANG ; Xuejun LIU ; Dan LI
Chinese Journal of Geriatrics 2025;44(1):51-59
Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.
2.Impact of nutritional factors on the prognosis of elderly patients with idiopathic pulmonary fibrosis
Shuhui XU ; Dandan CHANG ; Bing WEN ; Dan LI ; Yufeng DU ; Li QIAN
Chinese Journal of Geriatrics 2025;44(12):1698-1705
Objective:To explore the impact of different nutritional statuses on the prognosis of elderly patients with idiopathic pulmonary fibrosis(IPF), and to provide a basis for early intervention of the nutritional status of elderly IPF patients.Methods:A retrospective analysis was conducted on 237 elderly patients clinically diagnosed with IPF who were admitted to the First Hospital of Shanxi Medical University from January 2018 to May 2024.The GLIM criteria were applied to diagnose malnutrition and classify its severity.The patients were divided into two groups: those without nutritional risk(Group A)and those with nutritional risk(Group B). Group B was further subdivided into three subgroups: patients with only nutritional risk(Subgroup B1), those with moderate malnutrition(Subgroup B2), and those with severe malnutrition(Subgroup B3). The study observed the clinical characteristics of elderly IPF patients and the impact of nutritional factors on hospital admission frequency, activities of daily living(ADL), and all-cause mortality.Results:A total of 237 patients was included, with 129 patients(54.43%)in Group A and 108 patients(45.57%)in Group B. Among them, there were 34 patients(14.35%)in Subgroup B1, 57 patients(24.05%)in Subgroup B2, and 17 patients(7.17%)in Subgroup B3.The number of hospitalizations was significantly higher in both Group B and Subgroup B3 compared to Group A(both P < 0.05). However, no significant differences were found in the number of hospitalizations between Subgroup B1 or Subgroup B2 and Group A. There was no significant difference in the reduction of ADL between Group B(including all its subgroups)and Group A. The risk of mortality significantly increased with the increase in the severity of malnutrition(all P<0.05). After adjusting for factors such as gender, age, polypharmacy, home oxygen therapy, self-care ability, days of hospital stay, number of hospitalizations, pulmonary function, and inflammatory factors, nutritional risk and the degree of malnutrition remained independent risk factors for all-cause mortality in elderly IPF patients. Conclusions:A significant proportion of elderly IPF patients were found to have nutritional risk or malnutrition.The number of hospitalizations was significantly correlated with the nutritional status of these patients.After adjusting for multiple relevant factors, nutritional risk and the severity of malnutrition remained independent risk factors for mortality in elderly IPF patients.Therefore, greater emphasis should be placed on nutritional assessment and early nutritional intervention in the management of elderly IPF patients, so as to prevent and reduce the occurrence of nutrition-related adverse events.
3.Impact of nutritional factors on the prognosis of elderly patients with idiopathic pulmonary fibrosis
Shuhui XU ; Dandan CHANG ; Bing WEN ; Dan LI ; Yufeng DU ; Li QIAN
Chinese Journal of Geriatrics 2025;44(12):1698-1705
Objective:To explore the impact of different nutritional statuses on the prognosis of elderly patients with idiopathic pulmonary fibrosis(IPF), and to provide a basis for early intervention of the nutritional status of elderly IPF patients.Methods:A retrospective analysis was conducted on 237 elderly patients clinically diagnosed with IPF who were admitted to the First Hospital of Shanxi Medical University from January 2018 to May 2024.The GLIM criteria were applied to diagnose malnutrition and classify its severity.The patients were divided into two groups: those without nutritional risk(Group A)and those with nutritional risk(Group B). Group B was further subdivided into three subgroups: patients with only nutritional risk(Subgroup B1), those with moderate malnutrition(Subgroup B2), and those with severe malnutrition(Subgroup B3). The study observed the clinical characteristics of elderly IPF patients and the impact of nutritional factors on hospital admission frequency, activities of daily living(ADL), and all-cause mortality.Results:A total of 237 patients was included, with 129 patients(54.43%)in Group A and 108 patients(45.57%)in Group B. Among them, there were 34 patients(14.35%)in Subgroup B1, 57 patients(24.05%)in Subgroup B2, and 17 patients(7.17%)in Subgroup B3.The number of hospitalizations was significantly higher in both Group B and Subgroup B3 compared to Group A(both P < 0.05). However, no significant differences were found in the number of hospitalizations between Subgroup B1 or Subgroup B2 and Group A. There was no significant difference in the reduction of ADL between Group B(including all its subgroups)and Group A. The risk of mortality significantly increased with the increase in the severity of malnutrition(all P<0.05). After adjusting for factors such as gender, age, polypharmacy, home oxygen therapy, self-care ability, days of hospital stay, number of hospitalizations, pulmonary function, and inflammatory factors, nutritional risk and the degree of malnutrition remained independent risk factors for all-cause mortality in elderly IPF patients. Conclusions:A significant proportion of elderly IPF patients were found to have nutritional risk or malnutrition.The number of hospitalizations was significantly correlated with the nutritional status of these patients.After adjusting for multiple relevant factors, nutritional risk and the severity of malnutrition remained independent risk factors for mortality in elderly IPF patients.Therefore, greater emphasis should be placed on nutritional assessment and early nutritional intervention in the management of elderly IPF patients, so as to prevent and reduce the occurrence of nutrition-related adverse events.
4.Professor Jin Shi Treats Vascular Intestinal Obstruction from the Perspective of Collaterals
Yufeng HU ; Xiaojin HE ; Feifei XI ; Xiangyu ZHANG ; Bin DU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1100-1107
Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.
5.Research on the mechanism of RNA m 6A modification in age-related idiopathic pulmonary fibrosis
Li QIAN ; Ziyue SUN ; Yongkang HAN ; Yufeng DU ; Xiaohui WANG ; Xuejun LIU ; Dan LI
Chinese Journal of Geriatrics 2025;44(1):51-59
Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.
6.Professor Jin Shi Treats Vascular Intestinal Obstruction from the Perspective of Collaterals
Yufeng HU ; Xiaojin HE ; Feifei XI ; Xiangyu ZHANG ; Bin DU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1100-1107
Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.
7.Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial.
Qinhua FAN ; Chongming WU ; Yawei DU ; Boyang WANG ; Yanming XIE ; Zeling ZHANG ; Wenquan SU ; Zizhuo WANG ; Changchang XU ; Xueke LI ; Ying DING ; Xinjiang AN ; Jing CHEN ; Yunying XIAO ; Rong YU ; Nan LI ; Juan WANG ; Yiqun TENG ; Hongfen LV ; Nian YANG ; Yuling WEN ; Xiaoli HUANG ; Wei PAN ; Yufeng LIU ; Xueqin XI ; Qianye ZHAO ; Changshan LIU ; Jian XU ; Haitao ZHANG ; Lie ZHUO ; Qiangquan RONG ; Yu XIA ; Qin SHEN ; Shao LI ; Junhong WANG ; Shengxian WU
Acta Pharmaceutica Sinica B 2024;14(12):5186-5200
The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.
8.Improvement effects of azithromycin on bronchopulmonary dysplasia in neonatal rats and its mechanism
Weina DU ; Shuqiang GAO ; Rong JU ; Yufeng XI
China Pharmacy 2024;35(2):155-159
OBJECTIVE To investigate the improvement effects of azithromycin on bronchopulmonary dysplasia (BPD) in neonatal rats based on hypoxia-inducible factor-1α(HIF-1α)/HIF-2α/vascular endothelial growth factor (VEGF) pathway. METHODS Sixty newborn SD rats were randomly divided into negative control group (NC), BPD group, azithromycin group and budesonide group (positive control), with 15 rats in each group. Rats in NC group were given normal breathing air, while rats in other three groups were exposed to high-concentration oxygen for 14 days to establish BPD rat models. After successful modeling, rats in azithromycin group were intraperitoneally injected with azithromycin 200 mg/kg, and rats in budesonide group were atomized with budesonide 1.5 mg/kg once a day for 14 consecutive days, while rats in BPD group and NC group were not treated. Pathological changes of lung tissue, radial alveolar count and mean alveolar intercept of rats were observed in each group. The white blood cell count in bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were detected; mRNA and protein expressions of VEGF, HIF-1α, HIF-2α were also detected. RESULTS Compared with NC group, the lung tissue in BPD group was obviously damaged; the white blood cell count, average alveolar intercept and the levels of TNF-α, IL-6, IL-1β and MDA were significantly increased; the radial alveolar count, SOD and CAT levels, the relative expressions of VEGF, HIF-1α, HIF-2α mRNA and protein were significantly decreased (P<0.05). Compared with BPD group, the changes of the above indexes in azithromycin group and budesonide group were significantly reversed (P<0.05). CONCLUSIONS Azithromycin can obviously improve the symptoms of BPD in rats, reduce inflammation and oxidative stress, and exert lung protection, the mechanism of which may be realized by activating HIF-1α/HIF-2α/VEGF pathway.
9.Effects of bacterial lysates on immune function in elderly mice with pulmonary fibrosis
Li QIAN ; Ziyue SUN ; Xiangrui GUO ; Dan LI ; Xuejun LIU ; Yongkang HAN ; Yufeng DU
Chinese Journal of Geriatrics 2024;43(2):209-215
Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.
10.Clinical efficacy and safety of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease treated with long-term home oxygen therapy
Bowen LIAN ; Yanyan ZHANG ; Jinchu GE ; Yufeng DU
Chinese Journal of Geriatrics 2024;43(10):1265-1270
Objective:To investigate the clinical efficacy and safety of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease(COPD)who are undergoing long-term home oxygen therapy.Methods:The study included a total of 60 elderly patients with COPD who were successfully discharged after receiving treatment at the First Hospital of Shanxi Medical University from November 2021 to October 2022.The enrolled patients were randomly divided into two groups: the pulmonary rehabilitation group and the control group, with 30 patients in each group.The allocation was determined using a random number table and prospective research methods.Patients in the pulmonary rehabilitation group underwent a 12-week pulmonary rehabilitation training program, while patients in the control group received pulmonary rehabilitation education and nutrition education.The general data of the two groups of patients were compared, including lung function parameters[forced expiratory volume in one second(FEV 1), forced vital capacity(FVC), forced expiratory volume in one second to forced vital capacity ratio(FEV 1/FVC), and percentage of predicted forced expiratory volume in one second(FEV 1%pred)], blood gas analysis[partial pressure of arterial oxygen(PaO 2), partial pressure of arterial carbon dioxide(PaCO 2), arterial oxygen saturation(SaO 2)], 6-minute walking distance(6MWD), grip strength, 5-round sit to stand test(5R-STST), modified British medical research council(mMRC)score, COPD assessment test(CAT)score, closed cycles test(CCT), Berg balance scale(BBS), and safety measures.These parameters were assessed before and after the intervention. Results:A total of 29 patients in the pulmonary rehabilitation group and 28 patients in the control group completed the study.The general data between the two groups showed no significant difference(all P>0.05).After the intervention, patients in the pulmonary rehabilitation group showed improvements in FEV 1/FVC, PaO 2, PaCO 2, SaO 2, 6MWD, grip strength, 5R-STST, CAT, CCT, and BBS( t=-2.242, -4.630, W=-3.439, t=-6.512, -10.563, -6.197, W=-3.968, t=10.847, -7.334, W=-4.189, all P<0.05).Additionally, 6MWD, CAT, and CCT showed significant improvement after the intervention compared to the control group( t=-2.104, 2.183, 2.106, all P<0.05).No training-related adverse effects were observed during the study. Conclusions:The 12-week pulmonary rehabilitation program is shown to be effective for elderly patients with COPD who are undergoing long-term home oxygen therapy.This program helps to improve respiratory function, systemic symptoms, exercise endurance, muscle strength, and balance function.It is designed to be simple and easy to implement, allowing patients to achieve their training goals and improve their clinical symptoms.Additionally, the program has been found to be safe and well-tolerated by patients, making it a valuable intervention that should be promoted and widely applied.

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