1.Values of non-invasive myocardial work and tissue motion annular displacement in evaluating anthracycline-induced cardiotoxicity
Wei HE ; Hong WEI ; Xiuli SUN ; Ying LIU ; Tao CONG ; Yunlong XIA
Chinese Journal of Clinical Medicine 2026;33(1):74-82
Objective To explore the clinical values of non-invasive myocardial work (MW) and tissue motion annular displacement (TMAD) in evaluation of anthracycline therapy-related cardiac dysfunction in patients with non-Hodgkin lymphoma. Methods A total of 62 patients with non-Hodgkin lymphoma who received standardized chemotherapy based on doxorubicin. Two and three dimensional transthoracic echocardiography, along with two dimensional speckle tracking echocardiography, were performed one day before chemotherapy and at 3, 6, and 9 months after chemotherapy to assess left ventricular ejection fraction, global longitudinal strain (GLS), MW parameters, and TMAD. Logistic regression analysis was used to evaluate the risk factors for cancer therapy-related cardiac dysfunction (CTRCD). The receiver operating characteristic curve was used to assess the diagnostic values of MW- and TMAD-related parameters for CTRCD. Results Compared to baseline, GLS, global work index (GWI), global constructive work (GCW), global work efficiency (GWE), TMAD at midpoint (TMADmid), and TMADmid percentage of left ventricular long-axis diameter (TMADmid%) decreased at 3 months after chemotherapy, while global wasted work (GWW) increased at 6 months after chemotherapy (P<0.05). Logistic regression analysis showed that the relative reduction in GLS and TMADmid% at 3 months after chemotherapy were independent predictors for CTRCD (P<0.05), while MW parameters were not independent predictors for CTRCD. GLS reduction≥10.3% and TMADmid% reduction≥15.8% at 3 months after chemotherapy predicted CTRCD with 0.866 and 0.824 of area under the curve (AUC), 92% and 75% of sensitivity, and 74% and 80% of specificity, respectively. AUC of combination of two indexes improved to 0.905, with 75% of sensitivity and 90% of specificity. Conclusions In non-Hodgkin lymphoma patients, the combination of GLS and TMADmid% is helpful of predicting CTRCD early, TMAD may be a novel diagnostic index for CTRCD, and GLS has superior predictive performance than MW for CTRCD.
2.Effects of oleic acid-induced lipid droplet synthesis on the proliferation,migration, invasion, and epithelial-mesenchymal transition of osteosarcoma cells
Mengting WANG ; Yunlong WANG ; Mengxia LIANG ; Jun LIU ; Erbao BIAN
Acta Universitatis Medicinalis Anhui 2026;61(1):9-15
ObjectiveTo explore the effects of different concentrations of oleic acid on human osteosarcoma cell lines 143B and HOS, as well as the impacts of the optimal concentration of oleic acid on cellular lipid droplet synthesis and cell functions. MethodsThe 143B and HOS cells were treated with varying concentrations of oleic acid (0, 25, 50, 100, and 200 µmol/L) for 48 hours. Following treatment, oil red O staining and BODIPY staining were performed to determine the optimal concentration. Subsequently, CCK-8 assays and colony formation experiments were conducted to assess the effect of this optimal concentration of oleic acid on the cell proliferation of both cell lines. Transwell migration assays were utilized to evaluate the influence of the optimal concentration on migratory capacity and Transwell invasion assays were utilized to evaluate the invasive ability. Additionally, Western blot analysis was employed to examine the expression levels of epithelial-mesenchymal transition (EMT) markers Epithelial cadherin (E-cadherin) and Neural cadherin (N-cadherin) in response to treatment with the optimal concentration of oleic acid. ResultsTreatment with oleic acid did not induce significant cell death in either 143B or HOS cells; however, an increase in intracellular lipid droplets was observed alongside enhanced proliferation, migration, invasion capabilities as well as EMT transformation potential (P<0.05). ConclusionOleic acid induces lipid droplet synthesis in osteosarcoma cells which subsequently promotes their proliferation, migration and invasion abilities along with EMT transformation.
3.Identification of core genes of osteoarthritis by bioinformatics
Xuekun ZHU ; Heng LIU ; Hui FENG ; Yunlong GAO ; Lei WEN ; Xiaosong CAI ; Ben ZHAO ; Min ZHONG
Chinese Journal of Tissue Engineering Research 2025;29(3):637-644
BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.
4.Open and minimally invasive treatment strategies for horseshoe kidney with hydronephrosis: efficacy analysis of isthmus resection
Zhaowei ZHU ; Yuan LIU ; Liyuan DUAN ; Yupeng LIU ; Jin TAO ; Yafeng FAN ; Yonghao ZHAN ; Yunlong LIU ; Shuanbao YU ; Xuepei ZHANG
Chinese Journal of Surgery 2025;63(12):1125-1130
Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.
5.HFA-ICOS score in predicting cancer therapy-related cardiac dysfunction among breast cancer and lymphoma patients
Chang SHAN ; Mingyue JU ; Mei YANG ; Yanli ZHANG ; Xinxin ZHANG ; Xuefu CHEN ; Jia LI ; Fengqi FANG ; Xiuli SUN ; Yunlong XIA ; Ying LIU
Chinese Journal of Cardiology 2025;53(8):882-890
Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.
6.MiR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11
Shuman ZHEN ; Haoran ZHANG ; Jiaxin SI ; Jiaqi WANG ; Yan ZHAO ; Yunlong JIA ; Lihua LIU
Chinese Journal of Oncology 2025;47(7):645-656
Objective:To investigate the effect of miR-1-3p on mitophagy in human esophageal squamous cell carcinoma (ESCC) cells and the related mechanisms.Methods:The differentially expressed miRNAs in ESCC were screened using the GEO database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-1-3p expression in normal esophageal epithelial cells (HET-1A) and ESCC cell lines (TE1, KYSE30, KYSE150, KYSE410, Eca109). Bioinformatics tools were utilized to predict target genes of miR-1-3p, subcellular localization was confirmed by fluorescence in situ hybridization. The targeting relationship between miR-1-3p and SLC7A11 was validated using dual-luciferase reporter assay. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Furthermore, experimental validation demonstrated that overexpression of SLC7A11 rescued the presence of the miR-1-3p/SLC7A11 axis. Confocal microscopy was used to detect changes in mitochondrial autophagic lysosomes, while transmission electron microscopy was employed to observe mitophagy and morphological alterations. Western blot was conducted to evaluate the expression of autophagy-related proteins LC3 and P62. Flow cytometry was used to measure mitochondrial membrane potential and reactive oxygen species (ROS). Immunohistochemistry was applied to assess SLC7A11 expression in 133 ESCC patient tissues and 115 normal esophageal epithelial tissues. The correlation between SLC7A11 expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for multivariate analysis.Results:The expression of miR-1-3p in ESCC cells was significantly lower than that in HET-1A cells ( P<0.05). SLC7A11 was a target gene of miR-1-3p. Transfection of miR-1-3p mimic inhibited the proliferation of ESCC cells. CCK-8 assay results showed that the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic group (absorbance values: 2.88±0.24 and 2.88±0.18, respectively) was significantly lower than that in the miRNA mimic negative control (NC) group (3.94±0.27, P<0.001; 4.20±0.21, P<0.001). Meanwhile, the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic+SLC7A11-overexpression (OE) group (absorbance values: 3.57±0.15 and 3.60±0.13, respectively) was significantly higher than that in the miR-1-3p mimic +empty vector (EV) group (2.54±0.10, P<0.001, 2.36±0.16, P<0.001). Additionally, transfection of miR-1-3p mimic promoted apoptosis. Flow cytometry results demonstrated that the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic group [(9.22±0.05)% and (6.55±0.37)%, respectively] were significantly higher than those in the miRNA mimic NC group [(0.81±0.17)%, P<0.001); (1.04±0.12)%, P<0.001]. Conversely, the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic + SLC7A11-OE group [(0.73±0.04)% and (1.19±0.05)%, respectively] were significantly lower than those in the miR-1-3p mimic+EV group [(9.83±0.41)%, P<0.001); (6.09±0.17)%, P<0.00)]. MiR-1-3p mimic downregulated SLC7A11 protein expression and the LC3Ⅱ/LC3I ratio ( P<0.05), upregulated P62 protein expression ( P<0.05), this phenomenon can be rescued by overexpressing SLC7A11 ( P<0.05). Additionally, miR-1-3p mimic increased ROS levels and decreased mitochondrial membrane potential (JC-1 aggregate/monomer ratio), this phenomenon can be rescued by overexpressing SLC7A11 ( P<0.05). SLC7A11 expression was higher in ESCC tissues compared to normal esophageal epithelial tissues ( P<0.001), and SLC7A11 serves as an independent prognostic factor in ESCC ( HR=2.15, 95% CI: 1.27-3.65, P=0.004). Conclusion:miR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11.
7.Real-world adverse event profile of trabectedin:A signal mining and spatiotemporal analysis based on FAERS database
Bowen ZHANG ; Ludan ZHANG ; Hongrui CHEN ; Chunxiao LYU ; Yunlong LIU ; Yang LUO ; Aruhan DONG ; Zhuting LI ; Yuhong HUANG ; Ruihua WANG
Journal of Army Medical University 2025;47(19):2425-2436
Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.
8.A Monte Carlo simulation-based study of 235U distribution effect on lung counter detection efficiency
Jie LIU ; Yunlong JI ; Xu XU ; Xiaomin ZHANG ; Dawei LI ; Yuxin ZHANG ; Jing NING
Chinese Journal of Radiological Medicine and Protection 2025;45(3):223-228
Objective:To investigate the effect of nuclide distribution with time from the in vivo metabolism based on measurement of radioactive contamination using lung counting method. Methods:The distribution of nuclides in the body with time was calculated on a basis of a single inhalation of aerosols containing 235U and the International Commission of Radiological Protection(ICRP) nuclide metabolism compartment model. A passive efficiency calibration of the lung counter, was performed using the simulation and calculation software Geant4 to obtain the contribution of the tissue or organs of interest to the lung counter, and to investigate the effect of the nuclide distribution on the lung counting method. Results:The time elapsed after inhalation of radionuclides, as well as their physicochemical state, has the effect on their distribution in the body and on the detection efficiency of the lung counter. Radionuclides with smaller particulate sizes have a higher initial retention in the lungs, and those with an activity median aerodynamic diameter (ADAM) of 1 μm contributed more fraction to the lung counter than those with an ADAM of 5 μm. F-type compounds were metabolized more rapidly by the respiratory system, and after 8 h of ingestion, nuclides were distributed in the lungs. F-type compounds were metabolized in the respiratory system at a relatively fast rate, and 8 h after inhalation, the fraction of nuclides retained in the lung contributed no more than 30% to the lung counter. Within 3 d after ingestion of M-type and S-type compounds, radioactive particulats largely deposites in the nasopharyngeal region. With biological metabolization and clearance, the fraction contributed by lung to counter is in rising, and the fraction to the lung counter typically remained larger than 80% after 3 d.Conclusions:Radionuclide metabolization in the body varies with their physicochemical properties and measurement time and site. For estimating internal contamination, consideration should be given to the distribution of nuclides, in order to avoid the overestimation.
9.Risk factors associated with non-radiographic bone erosion in patients with gout
Wei LIU ; Wen GUO ; Zhe GUO ; Chunyan LI ; Yunlong LI ; Siqi LIU ; Liang ZHANG ; Hui SONG
Journal of Peking University(Health Sciences) 2025;57(4):735-739
Objective:To analyze the factors associated with non-radiographic bone erosion in gout pa-tients,to improve the understanding of bone erosion in gout,and to promote the early detection of bone erosion.Methods:A retrospective analysis was conducted on the medical records of gout patients treated at Beijing Jishuitan Hospital from January 2018 to January 2022.Bone erosion was detectable by ultra-sound but not detected by X-ray as non-radiographic bone erosion;no bone erosion was detected by both ultrasound and joint X-ray as undetected bone erosion.A case-control study was used,and the two groups were matched 1∶2 according to age and sex.The differences between the two groups were com-pared in terms of general information,joint involvement characteristics,laboratory indicators and compli-cations.In the univariate analysis,P<0.1 was included in the multivariate analysis,and the conditional Logistic regression was used for the multivariate analysis.P<0.05 was considered to have statistically significant differences.Results:Among the 41 patients with non-radiographic bone erosion,the top three joints with bone erosion before its occurrence were metatarsophalangeal joint(12 cases),ankle(10 ca-ses),and knee(7 cases).There were 82 patients undetected with bone erosion.There were no signifi-cant differences in general information between the two groups(P>0.05),including age,gender,body mass index,and alcohol consumption history.The characteristics of affected joints in the non-radio-graphic bone erosion group were compared with those in the no bone erosion detected,and the former had more affected joints(P=0.02),and a higher proportion of patients with at least 3 attacks of gout per year(P<0.001).There were no significant differences in serum uric acid,fasting blood glucose,cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,creatinine,homocysteine,white blood cell count,and urine pH between the two groups(P>0.05).The results of multivariate analysis showed that at least 3 flares of gout per year was an independent risk factor for radiologically negative bone erosion in patients with gout,with an OR(95%CI)of 5.139(1.529-17.271).Conclusion:At least 3 flares of gout per year predicts the occurrence of radiologically negative bone erosion,and these patients should be given more attention to achieving treatment targets.
10.Mediating effects of cardiovascular health status in association between educational level and cardiovascular disease
Yanan WU ; Minhua TANG ; Biying WANG ; Yiling WU ; Liping YI ; Hongjie YU ; Yunlong KAN ; Shuai ZHU ; Xiaohua LIU ; Yonggen JIANG ; Genming ZHAO
Chinese Journal of Epidemiology 2025;46(5):840-849
Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

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