1.Effects of Autonomic Neuromodulators on Atrial Electrical Remodeling and Histopathological Changes in a Rat Model of Atrial Fibrillation
Jiafei LI ; Zhenhao ZHANG ; Shuo WANG ; Ge TIAN ; Shuang WEN ; Yuxue YAN ; Ran CUI ; Zhen YE ; Yongchun CUI
Laboratory Animal and Comparative Medicine 2026;46(3):321-331
ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.
2.Temporomandibular joint capsule suspension for neocondyle stability in free fibular flap reconstruction of the mandibular condyle
Shuang BAI ; Yao YU ; Wen-Bo ZHANG ; Ya-Qing MAO ; Yang WANG ; Chi MAO ; Dian-Can WANG ; Xin PENG
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2025;51(1):46-53
Objectives:
This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle.
Patients and Methods:
Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery.
Results:
Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively).
Conclusion
The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.
3.Study on weight assignment of home care service quality indicators for the disabled elderly in Beijing based on the game theory
Tiancheng ZHANG ; Wen BAI ; Zhengwen FENG ; Hui LI ; Xiaolei CHEN ; Shuang SHAO ; Juan DU
Chinese Journal of General Practitioners 2025;24(3):279-287
Objective:To determine the weight coefficient of home care service quality indicators for the disabled elderly in Beijing.Methods:In the early stage, our research group has preliminarily constructed quality indicators of home care service for the disabled elderly in Beijing. The importance scores of all indicators were obtained through expert consultation from September to October 2021. Based on the game theory, the subjective and objective weighting methods were integrated to quantify the combinatorial optimization weight assignment of those indicators, in which the subjective weighting was calculated by proportional distribution method, and the objective weighting was obtained by entropy weight method.Results:The subjective weight assignments of the first-level indicators “service conditions”“service process” and “service outcome”were 0.332 2, 0.338 9, and 0.328 9, respectively; the objective weight assignments of the above indicators were 0.332 2, 0.338 9 and 0.328 9, respectively; the combinatorial optimization weight assignment of those indicators were 0.332 2, 0.338 9, and 0.328 9, respectively. Among the second-level indicators, the combination optimization weight coefficients of the top 3 important indicators “patient family evaluation”(1.3),“emergency configuration”(1.4), and“operation process”(2.2) were 0.198 4, 0.198 4 and 0.170 8, respectively. And among the third-level indicators, the combination optimization weight coefficients of the top 5 important indicators“emergency plan”(1.4.1), “humanistic care”(2.2.6), “first aid supplies”(1.4.2), “evaluation of potential resources”(1.3.4), and “means of home visit transportation”(1.2.1) were 0.124 7, 0.075 0, 0.073 8, 0.066 5 and 0.052 7, respectively.Conclusion:The study has successfully conducted the optimization weight assignment of home care service quality indicators for the disabled elderly in Beijing, which indicates that the service conditions and service process are crucial to the quality of service.
4.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
5.Effects of Total Body Irradiation with 60 Co Gamma Ray at Different Dose Rates on Hematopoietic and Immune Cells in Mice.
Hui SHU ; Ya DONG ; Xue-Wen ZHANG ; Xing SHEN ; Shuang XING ; Zu-Yin YU
Journal of Experimental Hematology 2025;33(4):1181-1189
OBJECTIVE:
To investigate the effect of irradiation dose rate of 60Co γ-ray on hematopoietic and immune cells in total body irradiation (TBI) mice.
METHODS:
After TBI with 8 Gy 60Co γ-ray at three irradiation dose rates of 0.027, 0.256 and 0.597 Gy/min, the survival and change of body weight of C57BL/6J mice were observed within 30 days. The peripheral blood parameters were examined at each time point within 30 days post-irradiation. The hematopoietic stem/progenitor cell counts of mice were examined on the 10th and 30th day post-irradiation by flow cytometry, as well as the proportions of immune cells in peripheral blood, bone marrow and spleen of mice on the 30th day post-irradiation.
RESULTS:
After TBI with 8 Gy 60Co γ-ray, the 30-day survival rate of high dose-rate group was 0, which was significantly lower than 90% of medium dose-rate group and 100% of low dose-rate group (both P < 0.001). The peripheral blood parameters of all three groups showed a sharp decline → low value → gradually recovering trend. The count of white blood cell, neutrophil, lymphocyte, red blood cell, platelet and hemoglobin level in the high dose-rate and medium dose-rate groups were significantly lower than those in the low dose-rate group on day 7-18 post-irradiation (all P < 0.05), but there were no significant differences between the high dose-rate and medium dose-rate groups (P >0.05). On the 10th day after irradiation, the proportion and number of bone marrow hematopoietic stem/progenitor cells (including LK, LSK, LT-HSC, ST-HSC, and MPP cells) in the low dose-rate and medium dose-rate groups were significantly decreased compared to those in the normal group (all P < 0.05), but there were no significant differences between the two groups (P >0.05). On the 30th day after irradiation, LSK, LT-HSC, ST-HSC and MPP cells in the low dose-rate group recovered to normal levels, while those in the medium dose-rate group were still significantly lower than those in the low dose-rate group (all P < 0.001). The results of bone marrow and peripheral immune cell tests on the 30th day after irradiation showed that the ratios of T and B lymphocytes in the low dose-rate and medium dose-rate groups were reduced compared to that in the normal group (both P < 0.05), while the ratio of neutrophils was increased (P < 0.01). The trend of changes in the spleen and peripheral blood was consistent.
CONCLUSION
The degree of hematopoietic and immune cell damage in mice after TBI with 8 Gy 60Co γ-ray is related to the dose rate, and low dose-rate irradiation can reduce the damage in the animal model. Therefore, choosing the appropriate dose rate of irradiation is a key factor in establishing an objective and reliable experimental animal model of irradiation.
Animals
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Mice
;
Whole-Body Irradiation
;
Gamma Rays
;
Mice, Inbred C57BL
;
Hematopoietic Stem Cells/radiation effects*
;
Cobalt Radioisotopes
;
Dose-Response Relationship, Radiation
;
Male
6.Effect and Safety of Fuzheng Huazhuo Decoction against Prolonged SARS-CoV-2 Clearance: A Retrospective Cohort Study.
Wen ZHANG ; Hong-Ze WU ; Xiang-Ru XU ; Yu-Ting PU ; Cai-Yu CHEN ; Rou DENG ; Min CAO ; Ding SUN ; Hui YI ; Shuang ZHOU ; Bang-Jiang FANG
Chinese journal of integrative medicine 2025;31(5):387-393
OBJECTIVE:
To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS:
This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded.
RESULTS:
A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed.
CONCLUSION
FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans
;
Drugs, Chinese Herbal/adverse effects*
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
COVID-19 Drug Treatment
;
SARS-CoV-2/drug effects*
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COVID-19/virology*
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Adult
;
Aged
;
Treatment Outcome
7.Application and effectiveness evaluation of resident clinical pharmacist-led medication therapy management model in geriatric cardiology departments
Jingwen GUO ; Wen TIAN ; Bochang ZHANG ; Lishuang CHANG ; Shuang CAI
China Pharmacy 2025;36(21):2718-2722
OBJECTIVE To investigate the effectiveness of resident clinical pharmacist-led medication therapy management (MTM) model in geriatric cardiology departments, and provide reference for optimizing resident pharmaceutical services. METHODS A retrospective cohort study was conducted, incorporating data from inpatients admitted to the Department of Cardiovascular Medicine in the Geriatric Medical Center of our hospital during March to August 2023 (conventional group, n= 903) and the same period in 2024 (MTM group, n=963). The conventional group received only standard pharmaceutical services (including prospective prescription review and retrospective order evaluation), while the MTM group received additional resident clinical pharmacist-led interventions-such as medication reconciliation, personalized therapeutic drug monitoring (TDM), standardized intravenous infusion management, and a four-stage closed-loop monitoring process-based on conventional care. The effectiveness of the MTM model was evaluated by comparing the primary outcome measures (e.g., intravenous infusion rate, TDM target attainment rate) and secondary outcome measures [e.g., incidence of drug-drug interactions (DDIs), incidence of grade 3 or higher acute kidney injury, average length of hospital stay, cholesterol, and medication cost per capita] between the two groups. RESULTS Compared with the conventional group, in terms of primary outcome indexes: both the overall intravenous infusion rate and the use rate of acid-suppressive injection were significantly lowered in the MTM group (P<0.05); serum concentration target attainment rates for digoxin and vancomycin were increased significantly (P<0.05). For secondary outcome indexes, the MTM group exhibited significant decreases in the work incidence of grade 3 or higher acute kidney injury, the incidence of DDIs, the rate of patients leaving the hospital against medical advice, alanine amino-transferase, aspartate transferase and the per capita total medication cost (P<0.05). Additionally, there was a notable increase in the creatinine, estimated glomerular filtration rate and a significant shortening of the per capita length of hospital stay (P<0.05). CONCLUSIONS The resident clinical pharmacist-led MTM model can significantly optimize medication therapy processes, enhance medication safety and cost-effectiveness, thus playing a positive role in promoting rational drug use and improving patient outcomes.
8.Application of Ammonia Solution Coprecipitation Method in Strontium Isotope Analysis
Wen-Gang LIU ; Shuang WEI ; Xiao-Wei ZHANG ; Jian ZHANG ; Hong-Ying ZHOU
Chinese Journal of Analytical Chemistry 2025;53(1):115-123
In the process of strontium(Sr)isotope analysis,the separation and purification of Sr are crucial for obtaining high-precision Sr isotope ratios.In this work,ammonia solution was used as a precipitating agent to initially separate and purify Sr from geological samples through coprecipitation,followed by the combination with cation-exchange resin to quickly and effectively obtain high-purity Sr components.The experimental conditions of ammonia coprecipitation reaction were optimized using typical high Rb/Sr ratio(mass ratio)standard sample JR-2.The results showed that using 3 mL of ammonia(1 mol/L)as the precipitating agent,at 120℃for 1 h,could effectively remove more than 90%of Rb,Na and K,with Sr recovery exceeding 95%.To verify the stability and applicability of this separation process,geological standard samples(JR-2,BCR-2,AGV-2,BHVO-2,GSP-2,W-2a)with different rock types and Rb/Sr ratios were practically validated.The results demonstrated that the coprecipitation process with ammonia solution removed more than 90%of Rb,Na and K,with Sr recovery greater than 95%.To further assess the applicability of this method for samples with high Rb/Sr ratios,Rb was added to the rhyolite standard material JR-2,adjusting its Rb/Sr ratio to 500.The results showed that this separation process could still effectively achieve the separation of Rb and Sr,and high-precision Sr isotope analysis results were successfully obtained by combining thermal ionization mass spectrometer(TIMS).Ammonia solution,as a precipitating agent,offered advantages such as low cost,low procedural blanks,simplicity,and a wide range of applicability.Therefore,the combination of ammonia solution coprecipitation and cation-exchange resin enabled rapid Sr purification from geological samples,providing a novel separation approach for high-precision Sr isotope analysis of samples with high Rb/Sr ratios,with broad application prospects.
9.Relationship between serum ROCK2,SDC-1,Apelin-13 expression and renal function and prognosis in patients with diabetes nephropathy
Hongjuan LI ; Wen LI ; Shuang REN ; Yinping MENG ; Liu ZHANG
International Journal of Laboratory Medicine 2025;46(22):2732-2737,2742
Objective To investigate the relationship between serum Rho-associated coiled coil containing protein kinase 2(ROCK2),syndecan-1(SDC-1),Apelin-13 and renal function and prognosis in patients with diabetes nephropathy.Methods From November 2019 to November 2021,153 patients with diabetic nephrop-athy admitted to the hospital were selected as the study group,and 153 patients with simple diabetes were se-lected as the simple diabetes group.Another 153 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.The levels of serum ROCK2,SDC-1 and Apelin-13 were determined by enzyme-linked immunosorbent assay.Pearson correlation analysis was used to analyze the correlations between the levels of serum ROCK2,SDC-1,and Apelin-13 and the clinical data of pa-tients with urinary nephropathy.Univariate and multivariate Logistic regression analyses were conducted to analyze the influencing factors of poor prognosis in patients with diabetic nephropathy.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum ROCK2,SDC-1 and Apelin-13 for poor prognosis of patients with diabetes nephropathy.Results Compared with the healthy control group,the levels of serum ROCK2 and SDC-1 in the simple diabetes group and the study group increased,the level of Apelin-13 decreased,the estimated glomerular filtration rate(eGFR)decreased,and the ratio of urinary albu-min to creatinine(UACR)increased,and the differences were statistically significant(P<0.05).The levels of serum ROCK2,SDC-1,Apelin-13 and UACR in the study group were higher than those in the simple diabe-tes group,while eGFR was lower than that in the simple diabetes group,and the differences were statistically significant(P<0.05).Pearson correlation analysis indicated that the levels of serum ROCK2,SDC-1,and Apelin-13 in the study group were negatively correlated with eGFR(P<0.05),and positively correlated with renal disease stage,creatinine,24-hour proteinuria,and UACR index(P<0.05).Compared with the good prognosis group,the levels of serum ROCK2,DCC-1,Apelin-13 and UACR in the poor prognosis group in-creased(P<0.05),and eGFR decreased(P<0.05).Univariate and multivariate Logistic regression analyses indicated that the levels of serum ROCK2,SDC-1,and Apelin-13 were all influencing factors for the prognosis of patients(P<0.05).ROC curve analysis indicated that the area under the curve(AUC)for the combined prediction of poor prognosis in patients by serum ROCK2,DCC-1,and Apelin-13 levels was significantly grea-ter than that by ROCK2(Z=2.854,P=0.004)and DCC-1(Z=2.426,P=0.015)and Apelin-13(Z=2.172,P=0.030)were predicted separately.Conclusion The serum ROCK2,DCC-1 and Apelin-13 levels in patients with diabetic nephropathy increase and are related to renal function.The combination of the three has a relatively high predictive efficacy for the prognosis of patients.
10.4'-O-methylbavachalcone improves vascular cognitive impairment by inhibiting neuroinflammation via EPO/Nrf2/HO-1 pathway.
Xin-Yuan ZHANG ; Chen WANG ; Hong-Qing CHEN ; Xiang-Bing ZENG ; Jun-Jie WANG ; Qing-Guang ZHANG ; Jin-Wen XU ; Shuang LING
China Journal of Chinese Materia Medica 2025;50(14):3990-4002
This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals
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Male
;
Rats, Sprague-Dawley
;
NF-E2-Related Factor 2/immunology*
;
Rats
;
Chalcones/administration & dosage*
;
Cognitive Dysfunction/metabolism*
;
Signal Transduction/drug effects*
;
Neuroinflammatory Diseases/drug therapy*
;
Heme Oxygenase-1/metabolism*
;
Humans
;
Heme Oxygenase (Decyclizing)/genetics*

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