1.Effects of aerobic exercise on cognitive function in elderly patients with bipolar disorder
Xiangjun ZHAO ; Yongli ZHANG ; Xiaoning HUO ; Xiping SHEN ; Xiaoli YANG ; Xirong QIAO ; Xingtong SHU
Sichuan Mental Health 2026;39(3):206-211
BackgroundBipolar disorder is a severe mental disorder characterized by alternating episodes of mania and depression. It has a high recurrence rate and a high rate of disability. Elderly patients often suffer from more severe cognitive impairment due to neurodegenerative changes. The clinical intervention for bipolar disorder mainly relies on drug treatment, but drugs have limited effects on improving cognitive function, and some drugs may even aggravate cognitive impairment. Aerobic exercise, as a non-drug intervention method, has shown positive effects in improving cognitive function in patients with mental disorders. However, there are still insufficient studies on elderly patients with bipolar disorder. ObjectiveTo explore the impact of aerobic exercise on the cognitive function of elderly patients with bipolar disorder, so as to provide references for the formulation of strategies to improve the cognitive function of this population. MethodsA randomized controlled trial was conducted. A total of 60 elderly patients who were hospitalized at the Third People's Hospital of Lanzhou from January 2024 to March 2025 and met the diagnostic criteria for bipolar disorder as defined in the International Classification of Diseases,tenth edition (ICD-10) were selected. They were divided into the study group and the control group, with 30 cases in each group, based on the random number table method. Both groups were given quetiapine fumarate tablets and magnesium valproate sustained-release tablets. The study group additionally received aerobic exercise (including slow walking, doing exercises, and running), three times a week, for 30 minutes each time. At the baseline and at the end of the 3rd, 6th, 9th, and 12th week of the intervention, the Hamilton Depression Scale -24 item (HAMD-24), the Young Manic Rating Scale (YMRS), the Montreal Cognitive Assessment (MoCA), and Wechsler Adult Intelligence Scale Revised in China (WMS-RC) were used for assessment. ResultsThe time effect of the HAMD-24 score was statistically significant (Wald χ2=124.564, P<0.01). The time effect of the YMRS score was also statistically significant (Wald χ2=145.608, P<0.01), and the interaction effect between time and group was statistically significant (Wald χ2=14.968, P<0.05). At the 3rd, 9th, and 12th week of the intervention, the YMRS score of the study group was lower than that of the control group in the same period, and the differences were statistically significant (P<0.05). The time effect and group effect of the MoCA score were both statistically significant (F=99.347, 16.623, P<0.01). The time effect, group effect, and interaction effect between time and group of the WMS-RC memory quotient were all statistically significant (F=64.678, 10.197, 12.472, P<0.01). At the 6th, 9th, and 12th weeks of the intervention, the MoCA score and WMS-RC memory quotient of the study group were higher than those of the control group, and the differences were statistically significant (P<0.05). ConclusionAerobic exercise may help improve the manic symptoms and cognitive functions (especially memory ability) of elderly patients with bipolar disorder. [Funded by Science and Technology Project of Gansu Province (number, 24JRRA775); Science and Technology Project of Lanzhou City(number, 2022-5-155)]
2.Banxia Xiexintang Affect PD-L1 Expression Induced by Gastric Cancer Cell-derived Exosomes in Bone Marrow Mesenchymal Stem Cells via Akt/c-Myc Signaling Axis
Wei ZHANG ; Xiping LIU ; Lijuan SHI ; Zhongbo ZHU ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):94-101
ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 (PD-L1) expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells (BMSCs) through the protein kinase B (Akt)/c-myelocytomatosis oncogene (c-Myc) signaling axis, and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal, model, Banxia Xiexintang (10% serum containing Banxia Xiexintang), PD-L1 monoclonal antibody (10% blank serum containing PD-L1 antibody), and combination (10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody) groups. The suspension of BMSCs was added to the upper chamber of each group, with the normal group receiving serum culture medium without exosomes in the lower chamber, and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group received 10% serum containing Banxia Xiexintang, 10% blank serum containing PD-L1 monoclonal antibody, and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody, respectively, in the upper chamber. After 96 h, BMSCs from the upper chamber were collected, and the protein levels of p-Akt, Akt, c-Myc, and PD-L1, as well as the mRNA levels of Akt, c-Myc, and PD-L1, were determined by Western blot and Real-time PCR, respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group, the model group showed increases in protein levels of p-Akt, c-Myc, and PD-L1, as well as mRNA levels of c-Myc and PD-L1 (P<0.05, P<0.01), and no significant change in the protein and mRNA levels of Akt. Compared with the model group, the Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group showed decreases in protein levels of p-Akt, c-Myc, and PD-L1 (P<0.01). In addition, they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group (P<0.05). Compared with the normal group, the model group showed increases in the number of migrating NCI-N87 and BMSCs (P<0.05, P<0.01). Compared with the model group, the Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group showed decreases in the number of migrating NCI-N87 and BMSCs (P<0.05, P<0.01), with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group (P<0.01). ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover, it has a synergistic effect when being used together with PD-L1, possibly related to the regulation of the Akt/c-Myc signaling axis.
3.Banxia Xiexintang Affect PD-L1 Expression Induced by Gastric Cancer Cell-derived Exosomes in Bone Marrow Mesenchymal Stem Cells via Akt/c-Myc Signaling Axis
Wei ZHANG ; Xiping LIU ; Lijuan SHI ; Zhongbo ZHU ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):94-101
ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 (PD-L1) expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells (BMSCs) through the protein kinase B (Akt)/c-myelocytomatosis oncogene (c-Myc) signaling axis, and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal, model, Banxia Xiexintang (10% serum containing Banxia Xiexintang), PD-L1 monoclonal antibody (10% blank serum containing PD-L1 antibody), and combination (10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody) groups. The suspension of BMSCs was added to the upper chamber of each group, with the normal group receiving serum culture medium without exosomes in the lower chamber, and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group received 10% serum containing Banxia Xiexintang, 10% blank serum containing PD-L1 monoclonal antibody, and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody, respectively, in the upper chamber. After 96 h, BMSCs from the upper chamber were collected, and the protein levels of p-Akt, Akt, c-Myc, and PD-L1, as well as the mRNA levels of Akt, c-Myc, and PD-L1, were determined by Western blot and Real-time PCR, respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group, the model group showed increases in protein levels of p-Akt, c-Myc, and PD-L1, as well as mRNA levels of c-Myc and PD-L1 (P<0.05, P<0.01), and no significant change in the protein and mRNA levels of Akt. Compared with the model group, the Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group showed decreases in protein levels of p-Akt, c-Myc, and PD-L1 (P<0.01). In addition, they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group (P<0.05). Compared with the normal group, the model group showed increases in the number of migrating NCI-N87 and BMSCs (P<0.05, P<0.01). Compared with the model group, the Banxia Xiexintang group, PD-L1 monoclonal antibody group, and combination group showed decreases in the number of migrating NCI-N87 and BMSCs (P<0.05, P<0.01), with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group (P<0.01). ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover, it has a synergistic effect when being used together with PD-L1, possibly related to the regulation of the Akt/c-Myc signaling axis.
4.Erratum to: Advantages of contrast-enhanced ultrasound in the localization and diagnostics of sentinel lymph nodes in breast cancer.
Qiuhui YANG ; Yeqin FU ; Jiaxuan WANG ; Hongjian YANG ; Xiping ZHANG
Journal of Zhejiang University. Science. B 2025;26(3):302-302
The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.
5.Effects of Yifei Jianpi Prescription on Airway Mucus Hypersecretion and Protein Expressions of EGFR/PKC/NF-κB Pathway in Rats with Acute Lung Injury
Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Xuhui ZHANG ; Xiping LIU ; Hongmei LI ; Shixia LI ; Shixin ZHOU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):83-90
Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.
6.Preliminary exploration of the efficacy and safety of sintilimab combined with bevacizumab in second-line treatment of malignant pleural mesothelioma
Meng JIANG ; Zhenhua ZHANG ; Yonglong YU ; Xiping ZHU ; Ting WEI ; Na WANG ; Yazhen WANG ; Wenting HUANG
Chinese Journal of General Practitioners 2025;24(6):728-733
Objective:To evaluate the efficacy and safety of sintilimab combined with bevacizumab in the second-line treatment of malignant pleural mesothelioma(MPM).Methods:This was a longitudinal study. Patients with MPM who had progressed after first-line treatment and were admitted to the Day-Care Outpatient Department of Medical Oncology, Ningguo People′s Hospital from February 2019 to February 2022 were included. General clinical data of the patients were collected at baseline. The patients were treated with the second-line treatment regimen of sintilimab (200 mg)+bevacizumab (15 mg/kg) on a 21-day cycle. Enhanced CT scans were performed every 3 cycles to evaluate the efficacy until tumor progression or death. Follow-up period ended in December 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and the best response of each patient was recorded. The objective response rate (ORR) and disease control rate (DCR) were calculated. Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), ranging from grade Ⅰto Ⅳ. Kaplan-Meier survival curves were used to analyze PFS and OS, and survival times were expressed as median values.Results:A total of 23 MPM patients were included, with the mean age of (55.04±13.27)years, 15 males, 8 females, 19 cases of epithelial type and 4 cases of non-epithelial type. The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 12 patients and 2 in 11 patients. There were 17 smokers and 6 non-smokers, 12 cases with PD-L1 positive and 11 cases with PD-L1 negative, and 6 cases with anti-angiogenic drugs and 17 cases without using anti-angiogenic drugs in the first-line treatment. Of the 23 patients, 1 achieved complete response (CR), 9 achieved partial response (PR), 7 had stable disease (SD), and 6 had progressive disease (PD). The ORR and DCR of the enrolled patients were 43.5% (10/23) and 73.9% (17/23), respectively. Kaplan-Meier survival analysis showed that the PFS of the enrolled patients was 7.50 (95% CI: 5.47-9.54) months, and the OS was 12.50 (95% CI: 1.07-23.93) months. The most common adverse reactions related to the treatment of sintilimab combined with bevacizumab were hypertension (14 cases (60.9%)), fatigue (10 cases (43.5%)), decreased appetite (8 cases (34.8%)), proteinuria (6 cases (26.1%)), pruritus (5 cases (21.7%)), constipation (4 cases (17.4%)) and nausea (3 cases (13.0%)), etc. Only 9 patients had grade Ⅲ adverse reactions (8 cases of hypertension and 1 case of nausea), and only 1 patient had grade Ⅳ adverse reaction (hypertension). Conclusion:Sintilimab combined with bevacizumab has some therapeutic effects on progressive MPM, and the adverse reactions are relatively mild.
7.Analysis of contract renewal willingness and influencing factors among rural order-oriented medical graduates between 2015-2023 in Shaanxi Province
Shuijuan ZHANG ; Minwen WANG ; Shuai HAO ; Xuekun ZHOU ; Gong FENG ; Ya LI ; Xiping YANG ; Weina AN ; Zhaoxiang YU
Chinese Journal of General Practitioners 2025;24(7):809-816
Objective:To understand the contract renewal willingness and its influencing factors among rural order-oriented medical students in Shaanxi Province. M ethods This study employed an explanatory sequential mixed methods design to examine contract renewal patterns among rural order-oriented medical graduates. From February to July 2024, a questionnaire survey was conducted among rural order-oriented medical students who graduated from 2015 to 2023 in Shaanxi Province. The participants were first stratified into three strata based on their year of graduation and stage of service, and one-third of each stratum was randomly selected as the research subjects. Univariate and multivariate analysis methods were used to explore the influencing factors of their willingness to renew their service in rural areas. Secondly, qualitative research methods were employed to conduct thematic interviews with 36 targeted medical students on the influencing factors of their willingness to renew their service. Results:A total of 513 valid questionnaires were collected during the quantitative research phase, including 224 males and 289 females. Of these, 14 were from the 2015-2017 cohort, 247 from the 2018-2020 cohort, and 252 from the 2021-2023 cohort. The results showed that only 30.4%(156/513) of the orientation medical students were willing to practice in primary care after the period of service. Univariate analysis showed that there were six factors related to the willingness to renew the contract, the consistency of the source and implementation of the contract, the completion of the standardized training of residents, the satisfaction with primary work, professional identity, the ability of primary diagnosis and treatment, and the training system and the suitability of primary work. Multivariate analysis showed that the willingness to renew the contract was significantly higher in the students who had the same place of origin and the place of performance( OR=1.7, 95% CI: 1.1-2.6, P=0.022). The willingness to renew the contract was significantly higher among students who participated in the standardized residency training than those who completed the training( OR=2.0, 95% CI: 1.3-3.0, P=0.003), and students with a better fit between the training system and working in primary care were more likely to renew their contract( OR=4.1, 95% CI: 2.8-6.0, P<0.001). Four themes were extracted from the interview: subjective factors, objective environment, policy factors and other factors. Conclusions:The study shows that improving the consistency of the source of students and the implementation of the contract, strengthening the standardized training of residents, and optimizing the adaptation of the training system to the primary work are the key measures to improve the willingness of directional medical students to renew their contract at the primary level.
8.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
9.Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
Xuedi ZHANG ; Huasui CUI ; Yeding SONG ; Haoyan CHEN ; Xiping CUI ; Fanghong LI ; Yunping MU ; Zijian ZHAO
Chinese Journal of Comparative Medicine 2025;35(8):29-38
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180~200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P<0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P<0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.
10.Exploration on the Effects of Shengxian Huaxian Prescription on Pulmonary Fibrosis with Regulating the Polarization of M2 Type Macrophages Based on STAT6/PPAR-γ Pathway
Hong YANG ; Shixin ZHOU ; Hongmei LI ; Yanlin WU ; Xiping LIU ; Zhongbo ZHU ; Xuhui ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(1):113-119
Objective To observe the synergistic effect of Shengxian Huaxian Prescription and its disassembled prescription on pulmonary fibrosis;To explore whether its mechanism is related to regulating the STAT6/PPAR-y pathway to promote polarization of M2 type macrophages towards M1 type.Methods Ten SD rats were randomly selected from 70 rats as blank group,and the remaining rats were re-established pulmonary fibrosis model by intratracheal infusion of bleomycin.After modeling,the rats were divided into model group,positive group,Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group,with 10 rats in each group.Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group were given 12.60,7.65,3.60 and 2.25 g/kg of corresponding TCM solution,respectively;the positive group was given 0.12 g/kg of pirfenidone suspension;the blank group and the model group were given equal volume of normal saline,once a day,for consecutive 28 days.The lung function of rats was detected,the contents of IL-6 and TGF-β1 in serum were detected by ELISA,the pathological changes in lung tissue were observed by Masson staining,the expression of CD68,iNOS and CD206,Arg-1 in lung tissue were detected by immunofluorescence,the expression of SOCS1,SOCS3,STAT6,p-STAT6 and PPAR-γ in lung tissue were detected by Western blot.Results Compared with the blank group,the PEF,PIF and EF50 in model group rats significantly decreased,and the contents of serum IL-6 and TGF-β1 significantly increased,Masson staining showed a large amount of collagen fiber deposition,Ashcroft score significantly increased,CD206,Arg-1,STAT6,p-STAT6,PPAR-y protein expression significantly increased(P<0.01),the expressions of SOCS1 and SOCS3 protein significantly decreased(P<0.01),while the expression of CD68 and iNOS were not significantly changed(P>0.05).Compared with the model group,the PEF,PIF and EF50 in all administration groups significantly increased,and the contents of serum IL-6 and TGF-β1 significantly decreased,collagen fiber deposition in lung tissue were decreased to varying degree,Ashcroft score significantly decreased,the expression of CD206,Arg-1,STAT6,p-STAT6 and PPAR-γ protein significantly decreased(P<0.01),the expressions of CD68,iNOS,SOCS1 and SOCS3 protein significantly increased(P<0.05).The above indicators showed the most significant changes in Shengxian Huaxian Prescription group,followed by Shengxian group(P<0.01,P<0.05).Conclusion Both Shengxian Huaxian Prescription and its disassembled prescription have anti pulmonary fibrosis effects,and their mechanism may related to regulating the STAT6/PPAR-y pathway and promoting polarization of M2 type macrophages towards M1 type.Shengxian Huaxian Prescription group has the best effect,while Shengxian group play an important role in the prescription,and the compatibility between each group has a synergistic effect.

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