1.Clinical Observation on 45 Cases of Chronic Obstructive Pulmonary Disease in the Stable Phase with Qi Deficiency,Blood Stasis and Phlegm Obstruction Syndrome with Auxiliary Treated with Jinwei Guben Decoction (金卫固本汤) Combined with Bailing Capsule (百令胶囊)
Deyu KONG ; Xudong ZHENG ; Huimin ZHOU ; Ruitao WANG ; Benzhang ZHAO ; Jianjun WU
Journal of Traditional Chinese Medicine 2025;66(4):367-375
ObjectiveTo observe the clinical efficacy of modified Jinwei Guben Decoction (金卫固本汤, MJGD) combined with Bailing Capsule (百令胶囊, BC) in the treatment of chronic obstructive pulmonary disease (COPD) patients in the stable stage with qi deficiency, blood stasis and phlegm obstruction syndrome, in addition to conventional western medicine treatment. MethodsA total of 102 patients with stable COPD and qi deficiency, blood stasis, and phlegm obstruction syndrome were included in the study. According to the patients'preferences, they were divided into treatment group (49 cases) and control group (53 cases). The control group received conventional western medicine treatment, while the treatment group was given MJGD (1 dose daily) combined with BC (2.0 g each time, three times a day) additionally. The treatment period was 3 months, and the patients were followed up for 1 year after the treatment. The acute exacerbation frequency (mild, moderate, severe) before treatment, during treatment, at 6-month follow-up, and at 1-year follow-up was compared between groups. Additionally, the lung function indicators such as FEV1, FEV1%pred, FVC, and FEV1/FVC ratio, traditional Chinese medicine (TCM) syndrome scores, modified British Medical Research Council (mMRC) dyspnea scale, and the COPD Assessment Test (CAT) scores before and after treatment were compared. A logistic regression model was constructed to analyze the impact of MJGD combined with BC on clinical efficacy. ResultsFour patients dropped out from the treatment group and eight from the control group, leaving 45 patients of each group for statistical analysis. The number of mild and moderate acute exacerbations in the treatment group was lower than that in the control group during the treatment period, at 6-month follow-up and within 1 year of follow-up (P<0.05) .The number of severe acute exacerbations was only lower in the treatment group than in the control group at 6-month follow-up (P<0.05). Compared with that before treatment, the number of acute exacerbations of all degrees in the treatment group was significantly reduced within 1 year of follow-up (P<0.05),while only the number of mild acute exacerbations in the control group was significantly reduced within 1 year of follow-up (P<0.05). The treatment group showed significant improvement in FEV1 and FEV1%pred and FEV1/FEV, while the control group showed a significant decline in FEV1 and FVC (P<0.05). After treatment, both groups showed significant reductions in TCM syndrome scores, including coughing, sputum, wheezing, chest tightness, shortness of breath, and fatigue, as well as mMRC and CAT scores (P<0.05), with the treatment group having significantly lower scores than the control group (P<0.05). The overall clinical effective rate of in the treatment group was 93.33% (42/45), significantly higher than that of the control group, 75.56% (34/45, P<0.05). Multivariate logistic regression analysis showed that the use of MJGD combined with BC (OR = 4.68, 95%CI: 1.15 - 19.09, P = 0.03) was positively correlated with clinical efficacy. ConclusionsIn addition to conventional western medicine treatment, the combination of MJGD and BC can reduce the frequency of acute exacerbations, delay the decline of lung function, improve clinical symptoms, and significantly enhance the clinical efficacy in patients with stable COPD and qi deficiency, blood stasis, and phlegm obstruction syndrome.
2.Clinical Efficacy of Jinwei Pingchuan Decoction in Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm-heat Obstruction in Lung Syndrome
Xudong ZHENG ; Deyu KONG ; Benzhang ZHAO ; Huimin ZHOU ; Ruitao WANG ; Jianjun WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):125-133
ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations, lung function, and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction, with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy, while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment: the number of acute exacerbations, lung function indices (forced expiratory volume in one second [FEV1], percentage of predicted value [FEV1%pred], forced vital capacity [FVC], and FEV1/FVC ratio), the degree of acute exacerbation, TCM syndrome score, COPD assessment test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC) score, C-reactive protein (CRP), and white blood cell (WBC) count. ResultsAfter 3 months of follow-up, the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values (P<0.05). After treatment, the treatment group had fewer acute exacerbations than the control group (P<0.05). The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values (P<0.05). After treatment, the degree of acute exacerbation in the treatment group was improved compared to the control group (P<0.05). Regarding lung function, FEV1, FEV1%pred, FVC, and FEV1/FVC ratio increased significantly in the treatment group compared with the pre-treatment values (P<0.05), and similar improvements were observed in the control group (P<0.05). After treatment, FEV1 and FVC were higher in the treatment group than the control group (P<0.05). Regarding TCM syndrome scores, the scores for individual symptoms such as wheezing, cough, expectoration, chest tightness, shortness of breath, and fatigue, as well as the total score, decreased significantly in the treatment group compared with the pre-treatment values (P<0.05). In the control group, the scores for cough, expectoration, chest tightness, fatigue, and palpitation, as well as the total score, also decreased (P<0.05). After treatment, the treatment group showed significantly lower scores for wheezing, cough, chest tightness, shortness of breath, and the total score than the control group (P<0.05). Regarding the CAT score, the scores for cough, expectoration, chest tightness, climbing stairs, going out, activity, and energy, as well as the total score, decreased significantly in the treatment group compared with the pre-treatment values (P<0.05). In the control group, the scores for cough, expectoration, chest tightness, sleep, energy, and the total score decreased (P<0.05). After treatment, the treatment group showed significantly lower scores for cough, expectoration, chest tightness, activity, and going out than the control group (P<0.05). Regarding the mMRC score, CRP level, and WBC count, all these parameters decreased significantly in the treatment group compared with the pre-treatment values (P<0.05), and similar reductions were observed in the control group (P<0.05). ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness, thereby enhancing the quality of life of patients.
3.Clinical Efficacy of Jinwei Pingchuan Decoction in Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm-heat Obstruction in Lung Syndrome
Xudong ZHENG ; Deyu KONG ; Benzhang ZHAO ; Huimin ZHOU ; Ruitao WANG ; Jianjun WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):125-133
ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations, lung function, and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction, with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy, while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment: the number of acute exacerbations, lung function indices (forced expiratory volume in one second [FEV1], percentage of predicted value [FEV1%pred], forced vital capacity [FVC], and FEV1/FVC ratio), the degree of acute exacerbation, TCM syndrome score, COPD assessment test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC) score, C-reactive protein (CRP), and white blood cell (WBC) count. ResultsAfter 3 months of follow-up, the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values (P<0.05). After treatment, the treatment group had fewer acute exacerbations than the control group (P<0.05). The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values (P<0.05). After treatment, the degree of acute exacerbation in the treatment group was improved compared to the control group (P<0.05). Regarding lung function, FEV1, FEV1%pred, FVC, and FEV1/FVC ratio increased significantly in the treatment group compared with the pre-treatment values (P<0.05), and similar improvements were observed in the control group (P<0.05). After treatment, FEV1 and FVC were higher in the treatment group than the control group (P<0.05). Regarding TCM syndrome scores, the scores for individual symptoms such as wheezing, cough, expectoration, chest tightness, shortness of breath, and fatigue, as well as the total score, decreased significantly in the treatment group compared with the pre-treatment values (P<0.05). In the control group, the scores for cough, expectoration, chest tightness, fatigue, and palpitation, as well as the total score, also decreased (P<0.05). After treatment, the treatment group showed significantly lower scores for wheezing, cough, chest tightness, shortness of breath, and the total score than the control group (P<0.05). Regarding the CAT score, the scores for cough, expectoration, chest tightness, climbing stairs, going out, activity, and energy, as well as the total score, decreased significantly in the treatment group compared with the pre-treatment values (P<0.05). In the control group, the scores for cough, expectoration, chest tightness, sleep, energy, and the total score decreased (P<0.05). After treatment, the treatment group showed significantly lower scores for cough, expectoration, chest tightness, activity, and going out than the control group (P<0.05). Regarding the mMRC score, CRP level, and WBC count, all these parameters decreased significantly in the treatment group compared with the pre-treatment values (P<0.05), and similar reductions were observed in the control group (P<0.05). ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness, thereby enhancing the quality of life of patients.
4.Effects of long non-coding RNA nuclear enriched abundant transcript 1 on the proliferation,apoptosis and migration of keloid fibroblasts
Yanfeng ZHANG ; Huimin ZHANG ; Xiang HE ; Yuping ZHENG
Chinese Journal of Tissue Engineering Research 2025;29(2):347-354
BACKGROUND:It has been elucidated that downregulation of nuclear enriched abundant transcript 1(NEAT1)inhibits the progression of keloid fibroblasts,but the exact mechanism is not fully understood. OBJECTIVE:To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1(lncRNA NEAT1)on the proliferation,apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4(USP4)axis. METHODS:Keloid fibroblasts were divided into five groups:si-NC group,control check group,si-NEAT1 group,si-NEAT1+miR-136-5p inhibitor group,and si-NEAT1+inhibitor-NC group.qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p;cell counting kit-8 assay and EDU staining were performed to measure cell proliferation;flow cytometry was performed to measure apoptosis;scratch-healing experiment was performed to measure cell migration;western blot assay was performed to measure the protein expressions of USP4,p27,Bax,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain;dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. RESULTS AND CONCLUSION:Compared with the si-NC group,the NEAT1 expression,absorbance value at 450 nm,percentage of EDU positive cells,scratch-healing rate,the protein expressions of USP4,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain decreased in the si-NEAT1 group(P<0.05),while the expression of miR-136-5p,apoptosis rate,and the protein expressions of p27 and Bax increased(P<0.05).miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts.There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4.To conclude,silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis..
5.Huayu Mingmu Prescription Downregulates PI3K/Akt/mTOR-HIF-1α/VEGFA Signaling Pathway to Intervene in Retinal Angiogenesis of DR Rats
Xiaoqiu MA ; Lei ZHAO ; Huimin ZHOU ; Fanghui ZHENG ; Guoqing YANG ; Tao ZUO ; Xiande MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):78-87
ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)-hypoxia inducible factor-1α/vascular endothelial growth factor A (HIF-1α/VEGFA) signaling pathway in diabetic retinopathy (DR) rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group, while the remaining 53 rats were fed a high-sugar, high-fat diet combined with low-dose streptozotocin (STZ) intraperitoneal injection to establish a type 2 diabetes mellitus (T2DM) rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model, low-dose, medium-dose, and high-dose groups of Huayu Mingmu prescription (9.29, 18.57, 37.14 g·kg-1), and a calcium dobesilate group (0.16 g·kg-1), with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography, and pathological changes in retinal tissue were evaluated using hematoxylin-eosin (HE) staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff (PAS) staining. Immunofluorescence (IF) was used to detect the expression of VEGFA and angiopoietin-2 (Ang-2) in retinal tissue. Western blot was employed to detect the protein expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. ResultsCompared with the normal group, the model group exhibited significant pathological changes in retinal tissue, including the appearance of acellular capillaries, as well as significant endothelial cell (E) proliferation and pericyte (P) loss (P<0.01). The E/P was significantly elevated (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly increased (P<0.01), and the expression of Ang-2 protein was significantly elevated (P<0.01). In contrast, retinal tissue in the treatment groups showed alleviated pathological changes, with reduced endothelial cell proliferation and pericyte loss (P<0.05, P<0.01). Among the treatment groups, the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly reduced (P<0.05, P<0.01), and the expression of Ang-2 protein was significantly decreased (P<0.01). ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats, delay the progression of DR, and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.
6.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
7.Role of insulin-like growth factor-Ⅰ in prognostic evaluation and treatment of liver cirrhosis
Yanping WANG ; Ya ZHENG ; Huifang ZHANG ; Huimin WANG ; Xiaotong MA ; Zhaofeng CHEN
Journal of Clinical Hepatology 2025;41(6):1188-1193
As a key member of the insulin-like growth factor family, insulin-like growth factor-Ⅰ (IGF-Ⅰ) is mainly synthesized in the liver and is widely distributed in the human body, and it is involved in the physiological processes such as cell proliferation, differentiation, metabolism, and apoptosis. Studies have shown that the level of IGF-Ⅰ is negatively correlated with the severity of liver cirrhosis, and IGF-Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis, promoting DNA damage repair, and regulating lipid metabolism. Monitoring of IGF-Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis, and stimulating the action pathway of IGF-Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-Ⅰ in liver cirrhosis, in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.
8.The current status and influencing factors of care preparedness in primary caregivers of hospitalized children with acute leukemia
Junxia WANG ; Hong ZHENG ; Huimin ZHANG ; Miaomiao YANG
Chinese Journal of Practical Nursing 2024;40(1):51-57
Objective:To investigate the current status and influencing factors of care preparedness in primary caregivers of children with acute leukemia, so as to provide theoretical basis for targeted nursing intervention plans in the future.Methods:A total of 160 primary caregivers of children with acute leukemia in Hematology Hospital of the Chinese Academy of Medical Sciences recruited by convenient sampling were investigated by the general data questionnaire, the Preparedness for Caregiving Scale, the Herth Hope Index, the Family Caregiver Task Inventory and the Mishel Uncertainty in Illness Scale-Family Member Form. Descriptive analysis, Mann-Whitney U test, Kruskal-Wallis H test, Spearman rank correlation and multiple stepwise liner regression were used for statistical analysis. Results:One hundred and fifty-nine questionnaires were effectively collected, including 13 males and 146 females, aged (34.61 ± 8.60) years old. The total score of care preparedness, hope, uncertainty in illness, care ability for caregivers were (26.47 ± 7.53), (37.72 ± 4.11), (61.96 ± 17.02), (15.06 ± 12.94) points. The total score of care preparedness for caregivers was negatively correlated with the score of uncertainty in illness( r=-0.300, P<0.05), and positively correlated with the hope and care ability of main caregivers ( r=0.166, 0.254, both P<0.05). Caregivers′ uncertainty in illness, caregiver gender, availability of other caregivers, caregivers′ hope entered the multiple stepwise regression equation, which could explain 20.4% of the total variation of resilience. Conclusions:The preparation of the primary caregivers for children with acute leukemia is at a medium level. The primary caregivers who are male, who have insufficient knowledge of the disease, who have no co-caregivers, and who have low hope level should be focused on in clinical practice. Pertinent measures should be taken to improve care preparedness and care quality.
9.Role of CIP2A in preoperative sleep deprivation-induced aggravation of postoperative cognitive dysfunction in aged mice
Yang LIU ; Huimin LI ; Hongyan GONG ; Miaomiao WEI ; Gaofeng ZHANG ; Mingshan WANG ; Fang ZHENG
Chinese Journal of Anesthesiology 2024;44(1):46-52
Objective:To evaluate the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in preoperative sleep deprivation (PSD)-induced aggravation of postoperative cognitive dysfunction (POCD) in aged mice.Methods:One hundred and ten healthy C57BL/6J mice of either sex, aged 18-20 months, weighing 29-35 g, were divided into 5 groups ( n=22 each) using a random number table method: sham operation group (S group), abdominal surgery group (O group), PSD + abdominal surgery group (D+ O group), CIP2A shRNA + abdominal surgery group (CS+ O group), and CIP2A shRNA+ PSD+ abdominal surgery group (CS+ D+ O group). At 14 days before surgery, control shRNA lentivirus was injected into the hippocampus in S, O and CS+ O groups, and CIP2A shRNA was injected into the hippocampus in D+ O and CS+ D+ O groups. PSD was carried out for 3 consecutive days prior to surgery. Cognitive function was assessed using the Morris water maze test at days 7-11 after surgery. The mice were sacrificed under deep anesthesia at day 3 after surgery, and hippocampal tissues were obtained to determine the expression of CIP2A, high mobility group box 1 (HMGB1), ionized calcium-binding adapter molecule 1 (Iba-1), alpha subunit of protein phosphatase 2A (PP2Aa), catalytic subunit of protein phosphatase 2A (PP2Ac), phosphorylated tau protein (p-tau) (S396), and p-tau (S404) (by Western blot), levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), and count of Iba-1 positive cells in the hippocampal CA1 region (using immunofluorescence staining). Results:Compared with S group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in O group ( P<0.05). Compared with O group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in D+ O group, and the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ O group ( P<0.05). Compared with D+ O group, the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ D+ O group ( P<0.05). There was no significant difference in PP2Aa expression among the five groups ( P>0.05). Conclusions:The mechanism by which PSD aggravates POCD is related to up-regulating the expression of CIP2A and promoting oxidative stress responses, neuroinflammatory responses and phosphorylation of tau protein in aged mice.
10.Effects of different concentrations of brusatol on silicosis fibrosis in mice
Huimin KANG ; Rou LI ; Hanqin WANG ; Yunfan ZHENG ; Shi CHEN
Journal of Environmental and Occupational Medicine 2024;41(5):539-545
Background Silicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO2). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. Objective To investigate the effects of different concentrations of Bru on SiO2-induced silicosis fibrosis in mice. Methods Thirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg−1), with 6 mice in each group. Except the control group, the remaining groups were established as SiO2-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL−1 SiO2 suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. Results Compared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). Conclusion Low and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO2-induced silicosis mice.

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