1.Organizational Readiness for Change and Factors Influencing the Implementation of Shared Medical Appointment for Diabetes in Primary Healthcare Institutions
Wei YANG ; Yiyuan CAI ; Jiajia CHEN ; Run MAO ; Lang LINGHU ; Sensen LYU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(2):479-491
The success of implementation research is closely tied to the institution's pre-implementation readiness. This study aims to explore the organizational readiness for change (ORC) and its influencing factors on primary healthcare settings in the implementation of the "Shared Medical Appointment for Diabetes (SMART) in China: design of an optimization trial" and to enhance ORC and provide insights to support the effective implementation of the program. Qualitative interviews and quantitative surveys were conducted to evaluate the ORC level and its influencing factors in 12 institutions implementing the SMART program. The Scale for Assessing the Institution's Readiness to Implement Evidence-Based Practices was utilized to measure ORC levels. Qualitative interviews were conducted among change implementers to gather information regarding the status of influencing factors. Thematic analysis was applied to extract factors from the interview data, and an assessment questionnaire was developed to measure the perceived impact of these factors. A fuzzy-set qualitative comparative analysis (fsQCA) method was employed to identify the influencing factors of ORC and pathways leading to high-level ORC. Seventy implementers from 12 institutions, encompassing administrators, clinicians, and health managers, participated in the interviews and surveys. The median and interquartile of the ORC scores were 105.20 (101.23, 107.33). The fsQCA indicated that a clear understanding of specific tasks and responsibilities, the active engagement of key participants, sufficient preliminary preparation, and the use of audits and feedback mechanisms were critical pathways to a high-level ORC. Conversely, institutions lacking key participants, preliminary preparation, or marginal influence demonstrated a low-level ORC. Before implementing innovation, Coherence and Cognitive Participation were identified as critical factors in influencing ORC. Strong leadership from key participants played pivotal role in enhancing readiness for change and was essential for improving implementation fidelity and overall program success.
2.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
3.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
4.Localization and Content Validation of the Organizational Readiness of Implementing Evidence-based Practices Scale
Jiajia CHEN ; Yiyuan CAI ; Wei YANG ; Run MAO ; Lang LINGHU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(3):765-776
This study aimed to localize the workplace readiness questionnaire (WRQ) and validate its applicability for assessing readiness for implementation of evidence-based practices (EBP) in primary care settings in China. The localization of the instrument will provide a practical instrument for assessing organizational readiness for change (ORC). The WRQ was translateed into Chinese version using the modified Brislin translation model, and its cross-cultural validity, content validity, and generalizability were evaluated by the Delphi method, and the expert feedback was evaluated using the item-level content validity index (I-CVI), scale-level content validity index (S-CVI), and corrected Kappa value. The index weights were evaluated by the analytic hierarchical process (AHP). The target users of the scale were invited to quantitatively evaluate its item importance score (IIS), and the surface validity was evaluated by combining the qualitative feedback from their cognitive interviews. To clarify the purpose of the scale, we revised its name to the Organizational Readiness of Implementing Evidence-Based Practices (ORIEBP) Scale. The ORIEBP scale contained five dimensions, which were Change Context, Change Valence, Information Evaluation, Change Commitment, Change Efficiency, and 32 items. After two rounds of the Delphi method to refine the construction of three dimensions and expressions of 11 items, the I-CVI were from 0.73 to 1.00, the Kappa value were from 0.70 to 1.00, and the S-CVI was over 0.92. All evaluation matrices of the hierarchical analysis method met the requirement of consistency ratio (CR < 0.1), and the weights of five dimensions were 0.2083, 0.2022, 0.1907, 0.2193, and 0.1795, in sequence. Nine out of eleven experts identified that items were applicable to other readiness assessment scenarios. The IIS scores for the five dimensions and 32 items were ranged from 2.93 to 3.54, and 2.71 to 3.42, presenting good face validity. The cognitive interview results showed that professional expressions were complex to understand. This study validated the ORIEBP scale and has good content validity and generalizability. The scale can be further improved by expanding its scope of use and validating its structure validity and reliability in different settings.
5.Mechanism of Buyang huanwu tang in improving idiopathic pulmonary fibrosis by delaying cellular senescence
China Pharmacy 2025;36(10):1186-1190
OBJECTIVE To investigate the improvement effect and mechanism of Buyang huanwu tang on idiopathic pulmonary fibrosis (IPF) model rats. METHODS The rats were randomly divided into normal group, model group, pirfenidone group (positive control, 0.162 g/kg), Buyang huanwu tang low-, medium- and high-dose groups (6.435, 12.87, 25.74 g/kg), with 6 rats in each group. Except for the normal group, IPF model was established in the remaining groups by intratracheal injection of bleomycin sulfate. On the second day after successful modeling, medication was administered once a day for 28 consecutive days. After the last medication, the appearance and morphology, pathological changes, and fibrosis status of the lung tissues in rats were observed. cyclin-dependent kinase inhibitor 2A (P16), P21, transforming growth factor-β1 (TGF-β1), Smad3, Smad7, epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase 12 (MMP-12), chemokine ligand 2 (CCL2) and interleukin-4 (IL-4) protein expression in lung tissue were all determined. RESULTS Compared with the normal group, the lung tissue of rats in the model group exhibited gray-white color, harder texture, obvious bruising and cysts. Additionally, alveolar septa were significantly thickened, their structural integrity severely compromised, accompanied by pronounced infiltration of inflammatory cells and severe pulmonary fibrosis. Collagen volume fraction, protein expressions of P16, P21, TGF-β1, Smad3, EGF, EGFR and (IL-4) in lung tissue significantly increased (P<0.05 or P<0.01), while Smad7, MMP-12 and CCL2 protein expressions were significantly decreased (P<0.05 or P<0.01). Compared with the model group, the appearance, pathological morphology, and fibrosis degree of rat lung tissue in Buyang huanwu tang groups were significantly improved, and the above quantitative indicators were significantly reversed (P<0.05 or P<0.01). CONCLUSIONS Buyang huanwu tang can ameliorate IPF in rats, and its underlying mechanism may be associated with the inhibition of TGF-β1/Smad signaling pathway activity and the attenuation of cellular senescence.
6.Network analysis of factors related to non suicidal self injury among middle school students in Guizhou Province
ZHAO Wenxin, TIAN Meng, CHEN Siyuan, WU Jinyi, GAO Ying, DENG Xiwen, ZHANG Wanzhu
Chinese Journal of School Health 2025;46(1):92-95
Objective:
To explore the relationship between related factors of non-suicidal self-injury behavior (NSSI) among middle school students in Guizhou Province, so as to provide the evidence for preventing high risk behaviors in adolescents.
Methods:
A stratified cluster random sampling method was used to select 1 034 junior and senior middle school students from Zunyi City, Qiannan Prefecture and Tongren City in Guizhou Province from April to October in 2023. Questionnaire survey was conducted to collect information including Adolescent Self injury Scale and Family Assessment Device. The R 4.4.1 software was employed for network analysis visualization, centrality indicators, and result stability assessment.
Results:
The detection rate of NSSI behavior among middle school students in Guizhou province was 29.6%, with a detection rate of 25.5% for boys and 33.1% for girls, showing a statistically significant difference ( χ 2=7.07, P <0.05). There were statistically significant differences in scores of emotional communication, egoism, family rules, positive communication, problem solving, expression of positive emotions and management of negative emotions self-efficacy, and bullying victimization in various dimensions between middle school students with and without NSSI ( Z =-13.66 to -7.05, P <0.01). NSSI among middle school students was positively correlated with social/relational bullying, depression and anxiety, and there were relatively close connections in the network ( r =0.35, 0.43, 0.42, P <0.01). Centrality indicators showed that the highest in strength and closeness centrality were stress ( Z =1.29, 1.58), the highest in betweenness centrality was for emotional communication ( Z =1.91), and the highest in expected influence index was for physical bullying ( Z =1.44)( P < 0.05).
Conclusions
Stress, emotional communication and physical bullying have significant impacts in the network of factors related to NSSI. Social/relational bullying, depression and anxiety have strong direct correlations with NSSI behavior among middle school students.
7.Prevalence of latent tuberculosis infection among freshmen in middle schools and their willingness of preventive treatment in Yunyan District of Guiyang
PENG Xiaowei, ZHANG Jiangping, LUO Peng, CHEN Siyin, XU Mengqun, WANG Qun
Chinese Journal of School Health 2025;46(1):129-133
Objective:
To investigate the status of latent tuberculosis infection(LTBI)among freshmen in middle schools and their willingness of preventive treatment in Yunyan District of Guiyang, so as to provide a reference for the prevention and control of tuberculosis in schools.
Methods:
The tuberculin skin test (TST) and X-ray scans were used to screen the TB infection of 13 915 freshmen in middle schools in Yunyan District of Guiyang in 2023, and a questionnaire survey on the willingness of accepting tuberculosis preventive treatment was conducted to LTBI patients. The χ 2 test and Fisher exact probability was conducted for the comparison of the rates among the groups.
Results:
Among the freshmen screened, the detection rate of LTBI was 3.29%. There were statistically significant difference in LTBI rates among freshmen of different genders (boys:2.87%, girls:3.81%), age groups (12-15 years old:3.31%, 16-17 years old:3.92%, 18-20 years old:1.91%), and school stages (junior high school:3.52%, ordinary high school:5.96%, vocational high school:2.29%)( χ 2=9.59, 13.08, 54.30, P <0.01). A total of 356 LTBI freshmen completed questionnaire survey,and 299(83.99%) were willing to accept tuberculosis preventive treatment, but the actual number of LIBI freshman who underwent preventive treatment was zero. Those LTBI who had received Bacille Calmette Guérin(BCG) vaccine(86.97%) was higher in the reporting rates of being willing to accept preventive treatment than that of LTBI who had not received BCG vaccine( 75.79 %),the differences were statistically significant( χ 2=6.48, P <0.05). The main reasons for refusing preventive treatment was worry about adverse drug reactions(80.70%), social acceptance and the support of social institutions were needed most(85.96%).
Conclusions
The LTBI rate among freshmen in Yunyan District of GuiYang is higher. Although the freshmen with LTBI have a higher willingness to accept preventive treatment, however, no one has undergone preventive treatment. Corresponding measures need to be taken for improving the preventive treatment rate of LIBI freshmen.
8.Health risk assessment of fluoride and trichloromethane in drinking water in rural schools in Guizhou Province
JIAN Zihai, ZHANG Jianhua, SU Minmin, CHEN Xuanhao, YUAN Minlan, YANG Dan, CHEN Gang
Chinese Journal of School Health 2025;46(1):134-137
Objective:
To analyze the distribution characteristics of fluoride and trichloromethane in drinking water in rural schools in Guizhou Province and assess their health risks, so as to provide a scientific basis for ensuring the safety of drinking water in rural schools.
Methods:
During the dry season (March to May) and wet season (July to September) of 2020 to 2022, 788 rural primary and secondary schools in agricultural counties (districts) in Guizhou Province were selected for investigation by using a direct sampling method. A total of 1 566 drinking water samples were collected from these schools, and the mass concentrations of fluoride and trichloromethane in the water samples were detected. The Mann-Whitney U test was used for intergroup comparison, and a health risk assessment model was employed to evaluate the health risks of students oral intake of fluoride and trichloromethane.
Results:
From 2020 to 2022, the mass concentrations of fluoride and trichloromethane in the drinking water of rural schools in Guizhou Province all met the standards, and the ranges were no detection to 0.99 mg/L and (no detection to 0.06)×10 -3 mg/L, respectively. The mass concentrations of fluoride in dry and wet seasons were 0.05(0.05,0.10), 0.05(0.05,0.10) mg/L, the mass concentrations of trichloromethane were [0.02(0.02,1.00)]×10 -3 , [0.02(0.02,1.00)]×10 -3 mg/L, the mass concentrations of fluoride in factory water and terminal water were 0.05(0.05,0.05), 0.05(0.05,0.10) mg/L, and the differences were not statistically significant ( Z=-0.04, -0.88, - 0.98 , P >0.05). There was a statistically significant difference in the mass concentration of trichloromethane between factory water and peripheral water [0.02(0.02,0.02)×10 -3 , 0.02(0.02,1.05)×10 -3 mg/L]( Z=-2.16, P < 0.05 ). The non-carcinogenic risk assessment values for students oral exposure to fluoride and trichloromethane were in the range of 0.01(0.01,0.03)-0.03(0.03,0.06) and [0.26( 0.26 ,14.54)]×10 -4 -[0.52(0.52,48.62)]×10 -4 , respectively, all of which were at acceptable levels; the carcinogenic risk assessment values for oral exposure to trichloromethane were in the range of [0.08(0.08, 4.51 )]×10 -7 -[0.16(0.16,15.07)]×10 -7 , indicating a low risk.
Conclusions
The health risks of students expore to fluoride and trichloromethane in drinking water in rural schools of Guizhou Province are low. It is necessary to strengthen the standardized management of disinfection in some rural drinking water projects and the monitoring of fluoride in water sources to reduce the exposure risk to children.
9.Mechanism of Modified Danggui Shaoyaosan in Improving Inflammation and Apoptosis in Acne via Regulating JNK/p38 MAPK Pathway
Gongzhen CHEN ; Yuqi YANG ; Xin LIU ; Ting TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):31-40
ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway. MethodsA rat ear acne model was established in SD rats, and the rats were divided into a blank group, a model group, and low-, medium-, and high-dose groups of modified Danggui Shaoyaosan (7.15, 14.30, 28.60 g·kg·d-1), with six rats in each group. After the administration for 14 consecutive days, morphological changes in the rats' auricles were observed, and hematoxylin-eosin (HE) staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the ear tissue. Quantitative reverse transcription polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression levels of Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), JNK, and p38 MAPK in the ear tissue. Additionally, Western blot analysis was conducted to assess the protein levels of Caspase-3, Bcl-2, Bax, JNK, and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group, rats in the model group exhibited redness, swelling, thickening, hardening, dryness, and roughness of the auricle. The surface showed sebaceous scales and desquamation, accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization, epidermal thickening, dermal collagen fiber degeneration and necrosis, subcutaneous muscle degeneration and necrosis, inflammatory cell infiltration, and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β, TNF-α, Caspase-3, Bax, JNK, and p38 MAPK were significantly increased (P<0.01), while those of Bcl-2 were significantly decreased (P<0.01). In comparison to the model group, the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle, with varying degrees of histopathological damage reduction. Additionally, the mRNA and protein expression levels of IL-1β, TNF-α, Caspase-3, Bax, JNK, and p38 MAPK in the tissue were significantly decreased (P<0.05, P<0.01), while those of Bcl-2 were significantly increased (P<0.05, P<0.01). Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin, kaempferol, luteolin, quercetin, wogonin, and baicalein. These compounds exerted their effects by modulating core targets such as TNF, IL-1β, Caspase-3, and Bcl-2, thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway, thereby alleviating inflammation and apoptosis.
10.Effect of Icariin on Myocardial Remodeling in Rats Based on Vitamin D Regulation of Dendritic Cell Phenotype
Qian LI ; Yujia CHEN ; Yan ZHOU ; Wen LI ; Liancheng GUAN ; Huanzhen WANG ; Yunzhi CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):76-85
ObjectiveTo investigate the effect of icariin (ICA) on the phenotype of dendritic cells (DCs) in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group, and male Dahl salt-sensitive rats were divided into a model group, low-, medium-, and high-dose ICA groups (30, 60, 120 mg·kg-1·d-1), and Vitamin D group (3×10-5 mg·kg-1·d-1). In addition to the normal group, the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored, and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 (Th17)/regulatory T cell (Treg) ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor (VDR), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), forkhead frame protein 3 (FoxP3), solitaire receptor γt (RORγt), myocardial type Ⅰ collagen (ColⅠ), and type collagen (ColⅢ) in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the normal group, the model group showed disordered arrangement and rupture of myocardial cells, nuclear condensation, significant edema of myocardial tissue, significant proliferation of collagen fibers in a network distribution, and a significant increase in tail artery blood pressure, left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD) (P<0.05). The phenotype of cardiac DCs was CD40, CD80, and CD86, and the levels of major histocompatibility complex Ⅱ (MHC-Ⅱ), Th17 cells, and Th17/Treg were significantly increased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt in the heart, as well as the mRNA expression of ColⅠ and ColⅢ, were significantly increased (P<0.05). The left ventricular ejection fraction (LVEF), interventricular septal thickness (IVSD), and left ventricular posterior wall thickness (LVPWD) were significantly decreased (P<0.05). The phenotype of cardiac DCs such as CD11, CD11b, and Treg cells, were significantly reduced (P<0.05), while the mRNA and protein expression of cardiac VDR, CYP27B1, and FoxP3 were significantly decreased (P<0.05). Compared with the model group, the low-, medium-, and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation, improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure, LVEDD, and LVESD were significantly decreased in the low-, medium-, and high-dose ICA groups and vitamin D group (P<0.05), and the phenotype of cardiac DCs including CD40, CD80, CD86, MHC-Ⅱ, Th17 cells, and Th17/Treg were significantly decreased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt, and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). The LVEF, IVSD, and LVPWD of myocardial remodeling model rats in the low-, medium-, and high-dose ICA groups and vitamin D group were significantly increased (P<0.05). The phenotypes of cardiac DCs including CD11, CD11b, and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group (P<0.05). The mRNA and protein expressions of VDR, CYP27B1, and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). ConclusionICA can regulate tail artery blood pressure, cardiac structural and functional damage, and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR, CYP24A1, and CYP27B1, achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.


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