1.Cordycepin Inhibits Fat Infiltration after Rotator Cuff Tear Injury by Regulating Wnt/β-catenin Signaling Pathway
Qiu'en XIE ; Dengwen LIANG ; Shao WU ; Xuhui HAO ; Liguang LIANG ; Bangxiang JIAN ; Junhong DONG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):98-106
ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway, providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study, with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose (20 mg·kg-1), medium-dose (40 mg·kg-1), and high-dose (80 mg·kg-1) cordycepin groups. After 6 weeks of treatment, the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the serum. Immunohistochemistry (IHC) was employed to detect the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of Wnt3a, Wnt10b, and β-catenin. ResultsCompared with the blank group, the model group showed decreases in stride length and paw print area (P<0.01), an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area (P<0.05), and decreased ratios of fat infiltration area and collagen fiber area (P<0.01). Additionally, the model group showed elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), up-regulated protein levels of PPARγ and C/EBPα (P<0.01), and down-regulated mRNA and protein levels of Wnt3a, Wnt10b, and β-catenin (P<0.05, P<0.01). Compared with the model group, the low-, medium-, and high-dose cordycepin groups showed increases in stride length and paw print area (P<0.01), a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area (P<0.05), and increases in ratios of fat infiltration area and collagen fiber area (P<0.05, P<0.01). In addition, cordycepin lowered the serum levels of IL-1β, IL-6, and TNF-α (P<0.05, P<0.01), down-regulated the protein levels of PPARγ and C/EBPα (P<0.01), and up-regulated the mRNA and protein levels of Wnt3a, Wnt10b, and β-catenin (P<0.05, P<0.01). ConclusionCordycepin can improve the limb function, alleviate rotator cuff muscle atrophy, fat infiltration, and fibrosis, and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.
2.Pharmacoeconomic evaluation of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy
Hai LIANG ; Runan XIA ; Panpan DI ; Mengmeng ZHAO ; Pengcheng ZHANG ; Yashen HOU ; Hong ZHANG ; Wei WU ; Miao YANG
China Pharmacy 2025;36(1):86-90
OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy (DN). METHODS From the perspective of healthcare service providers, a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months, a simulation period of 15 years and an annual discount rate of 5%. At the same time, one-way sensitivity analysis and probability sensitivity analysis were performed, and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan, and the accumulative utility was 8.052 4 quality-adjusted life year (QALYs); the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan, and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value, DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio, but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients, finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.
3.A Cross-sectional Study of Blood Glucose and Biochemical Indicators in Pediatric Patients with Hepatic Glycogen Storage Disease
Ni MA ; Haotian WU ; Ying WANG ; Jing YANG ; Danxia LIANG ; Min YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):132-137
ObjectivePatients with hepatic glycogen storage disease(GSD)have recurrent episodes of hypoglycemia. This study aimed to investigate and analyze blood glucose and biochemical indicators in pediatric patients with hepatic GSD, thus provide data support for hypoglycemia prevention and its clinical management. MethodsA cross-sectional field study was conducted among patients with hepatic GSD treated in the Department of Pediatrics of Guangdong Provincial People's Hospital on July 14, 2024. We collected the peripheral blood samples of the patients and their healthy family controls on site, then analyzed and compared their blood glucose and biochemical indicators. ResultsOf the 44 patients with hepatic GSD, there were 34 males and 10 females, including GSD Ib(n =14), GSD Ia(n=15), GSD Ⅲ(n=2), GSD Ⅵ(n=7)and GSD Ⅸ(n=6). The average age was 7.60(5.08-11.98)years. All patients were on uncooked cornstarch(UCCS)therapy. Of the patients, 77.3%(34/44)had hepatomegaly, 61.4%(27/44)had recurrent hypoglycemia, 61.4%(27/44)had blood glucose ≤ 3.9 mmol/L, 18.2%(8/44)had blood glucose ≤ 2.8 mmol/L, and none of the 8 cases was GSD Ib. The lowest blood glucose level was 1.19 mmol/L and no episodes of hypoglycemia occurred. Of the family control subjects, 65.9%(29/44)had blood glucose ≤ 3.9 mmol/L. There was no significant difference in hypoglycemia prevalence between hepatic GSD group and control group(P=0.658). The hepatic GSD patients had hyperlactacemia, hyperuricemia and hypercholesterolemia prevalence rates of 65.9%, 45.5% and 9.1%, respectively, as compared with 18.2%, 43.2% and 15.9%, respectively, for the family control subjects. No significant difference was found in the prevalence rates of hyperuricemia and hypercholesterolemia between the two groups(P=0.830 and P=0.334, respectively). ConclusionsAsymptomatic hypoglycemia is common in patients with hepatic GSD, especially in non-GSD-Ib patients. It is necessary to optimize the diet management of UCCS, conduct dynamic blood glucose monitoring and follow a light diet, so as to decrease hyperuricemia and hypercholesterolemia, avoid and reduce the serious adverse reactions and complications caused by severe hypoglycemia.
4.Evaluation of the performance of the artificial intelligence - enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula
Jihua ZHOU ; Shaowen BAI ; Liang SHI ; Jianfeng ZHANG ; Chunhong DU ; Jing SONG ; Zongya ZHANG ; Jiaqi YAN ; Andong WU ; Yi DONG ; Kun YANG
Chinese Journal of Schistosomiasis Control 2025;37(1):55-60
Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ2 = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ2 = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ2 = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ2 = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ2 = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ2 = 5.604, Padjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.
5.Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
Zhen NIU ; Xiaojie WU ; Liang YANG ; Zhixuan MA ; Junxiong YANG ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):293-300
ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis (AC) infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum, aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group (n=6) and an infection group (n=6). The infection group was orally administered 30 third-stage larvae of AC, while the control group received an equal volume of saline. Body weight, visual function, and behavioral scores were measured on post-infection 3, 6, 9, 12, 15, 18, and 21 days to assess neurological alterations. After 21 days, brain tissues were harvested for immunofluorescence staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed, and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection, Balb/c mice showed a decline in neurological behavioral scores (P<0.05). By day 15, visual scores decreased (P<0.05), and by day 21, significant weight loss (P<0.001) and mortality were observed. Concurrently, transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes (P<0.001). HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites, with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE (20:2) was significantly upregulated (P<0.001), while phosphatidylmethanol (18:0_18:1) was significantly downregulated (P<0.01). KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis, bile secretion, and cholesterol metabolism, and were involved in key metabolic pathways such as sphingolipid metabolism, neural signal regulation, and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways, modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways, particularly the dysregulation of cholesterol and sphingolipid metabolism, potentially playing a central role in demyelination onset. Furthermore, alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.
6.Effectiveness of the integrated schistosomiasis control programme in Sichuan Province from 2015 to 2023
Chen PU ; Yu ZHANG ; Jiajia WAN ; Nannan WANG ; Jingye SHANG ; Liang XU ; Ling CHEN ; Lin CHEN ; Zisong WU ; Bo ZHONG ; Yang LIU
Chinese Journal of Schistosomiasis Control 2025;37(3):284-288
Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ2 = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm2 in Sichuan Province from 2015 to 2023, with 204 602.81 hm2 treated by chemical control and 4 637.74 hm2 by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm2 in 2016 to 3 709.72 hm2 in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm2 in 2016 to 473.09 hm2 in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m2). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm2, hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm2, renovation of snail control forests covering 8 720 hm2 and newly building of shelterbelts covering 764 686.67 hm2. All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.
7.Sleep status in patients with Parkinson's disease and its relationship with dyskinesia and negative emotions
Min WU ; Liang ZHONG ; Heng LIN ; Xi YANG
Journal of Public Health and Preventive Medicine 2025;36(4):51-54
Objective To understand the sleep status in patients with Parkinson's disease (PD), and to explore its relationship with dyskinesia and negative emotions. Methods A total of 308 patients with PD who met the inclusion and exclusion criteria in the hospital from September 2022 to May 2024 were selected as the research subjects. The scores of sleep status [Pittsburgh Sleep Quality Index (PSQI)], dyskinesia [Simplified Fugl-Meyer Motor Assessment (FMA)] and negative emotions [Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II)] were analyzed, and the PSQI score was compared among patients with different demographic characteristics. Pearson correlation analysis was performed to analyze the correlation of sleep with dyskinesia and negative emotions in patients with PD. Results The total score of PSQI scale was (6.16±0.97) points in 308 PD patients, of which 208 cases (67.53%) were complicated with sleep disorders. The proportions of female, 61-75 years old, technical secondary school or below, disease course of 4 years and above, Hoehn-Yahr stage IV and unmarried status in the sleep disorder group were higher than those in the non-sleep disorder group (P<0.05). Compared with the non-sleep disorder group, the FMA score in the sleep disorder group was lower (P<0.05) while the BAI score and BDI-II score were higher (P<0.05). Pearson correlation analysis revealed that PSQI was negatively correlated with FMA (r=-0.489, P<0.05), and was positively correlated with BAI and BDI-II (r=0.476, 0.502, P<0.05). Conclusion The incidence rate of sleep disorders in PD patients is high. PSQI is negatively correlated with FMA, and is positively correlated with BAI and BDI-II.
8.Surveillance results of common diseases among primary and secondary school students in Yichang City in 2019 - 2022
Yi LIANG ; Zaoxia WANG ; Chi HU ; Xiaoyan MING ; Man XIAO ; Qian WU ; Zhongcheng YANG
Journal of Public Health and Preventive Medicine 2025;36(4):98-101
Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The “tripartite linkage” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.
9.Epidemiological analyses of 125 cases of paragonimiasis in Sichuan Province from 2020 to 2023
Yu ZHANG ; Yang LIU ; Liang XU ; Xiaohong WU ; Nannan WANG ; Lin CHEN
Shanghai Journal of Preventive Medicine 2025;37(6):511-514
ObjectiveTo analyze the epidemiological and clinical characteristics of paragonimiasis cases in Sichuan Province, and to provide an evidence for the prevention, diagnosis and treatment of paragonimiasis in medical institutions. MethodsData were collected from case reports submitted by cities (prefectures) from 2020 to 2023, including demographic information, epidemiological features, clinical symptoms, laboratory testing indicators, and awareness of paragonimiasis. Epidemiological descriptions and statistical analyses were performed on these variables. ResultsA total of 125 paragonimiasis cases were reported in Sichuan Province from 2020 to 2023, including 53 thoracic/pulmonary cases and 72 extrapulmonary cases. Geographically, cases were distributed in Dazhou City (63 cases, 50.40%), Yibin City (61 cases, 48.80%), and Deyang City(1 case, 0.80%). The male-to-female ratio was 1.66∶1, with 77.60% (97 cases) aged 0‒18 years. Students accounted for the majority of cases (67 cases, 53.60%). Among the patients, 67 cases (53.60%) had a history of consuming raw or undercooked crabs, and 94 cases (75.20%) reported drinking untreated water. The predominant symptoms included migratory subcutaneous nodules (26.40%), cough (24.80%), and abdominal pain/diarrhea (21.60%). Younger patients exhibited a higher proportion of migratory subcutaneous nodules, while older patients more frequently presented with cough and chest pain (χ2=4.060, P=0.044; χ2=9.235, P=0.002). Elevated eosinophil percentages and absolute counts were observed in 99.20% (124 cases) and 93.60% (117 cases) of patients, respectively. Peripheral white blood cell counts were higher in thoracic/pulmonary cases than that in extrapulmonary cases (Z=2.398, P=0.016), but no statistically significant differences were found in eosinophil absolute counts or percentages between the two types (Z=0.609, P=0.542; Z=0.732, P=0.464). In terms of treatment courses, 28 cases had 1 course, 31 cases had 2 courses, 43 cases had 3 courses, 11 cases had 4 courses, and 10 cases had 5 courses or more. Extrapulmonary cases required significantly longer treatment durations than thoracic/pulmonary cases (t=2.299, P=0.023). Only 12.80% (16 cases) of patients were aware of paragonimiasis. ConclusionParagonimiasis in Sichuan Province occurred sporadically, and the patients were mainly children and adolescents. The clinical manifestations of the patients lacked specificity, making it easy to lead to misdiagnosis. During the diagnosis, epidemiological history, migratory subcutaneous nodules and other main symptoms should be fully considered. An increase of the absolute count and proportion of eosinophils served as significant warning indicators for paragonimiasis infection.
10.Study on the effect and mechanism of Xinyang Tablet on myocardial ferroptosis in mice with chronic heart failure
Jinhua KANG ; Pengpeng LIANG ; Xiaoxiong ZHOU ; Ao LIU ; Zhongqi YANG ; Hongyan WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):516-528
Objective:
Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure.
Methods:
Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue.
Results:
Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05).
Conclusion
Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.


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