1.Reactive and Enzyme-activated Probe Strategies for Imaging Acute Kidney Injury
Ru-Long CHEN ; Ting-Fei XIE ; Jin-Xin ZHANG ; Jia-Ting CHEN ; Jie LI ; Peng-Fei ZHANG ; Ji-Hong CHEN ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(6):1622-1637
Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.
3.Research progress on the health communication capacity of clinicians
Dingbin CAI ; Luis Manuel Dias MARTINS ; Zefeng LU ; Sanhao HUANG ; Shuangmiao WANG ; Qini HUANG ; Zhaoji LONG ; Xinxin CHEN ; Siyang YE ; Dong WANG
China Occupational Medicine 2025;52(2):216-221
Health communication aims to improve public health attitudes and behaviors by propagating health information. It plays an important role in promoting public health literacy and "Healthy China Initiative". The basic theories of health communication include "7 W" and Theory of Planned Behavior. Clinicians with profound medical expertise and a wealth of clinical practice play key roles in the communication, and they hold an unparalleled advantage in health communication by delivering authoritative and trustworthy information to the public. The capacity of health communication among clinicians in the nation is determined by various factors including professional characteristics, policy support, dissemination platforms and pathways, time and effort. Meanwhile, some problems in the research on the health communication capacity of clinicians remain, such as lack of well-established motivation systems, limited dissemination pathways, and imperfect evaluation frameworks. In some regions of China, health communication performance has been considered as part of the professional title evaluation for clinical physicians. Medical institutions and universities have also initiated relevant training and practice programs. It is crucial to improve evaluation frameworks, strengthen training pathways and effectiveness assessment, promote interdisciplinary integration, and enhance the role of clinicians in health communication in the future.
4.Mechanism of Guben Jiannao Liquid on Alzheimer's disease by regulating autophagy based on LKB1/AMPK/mTOR pathway.
Jing-Fan ZHANG ; Qing-Hua LONG ; Chu-Hua ZENG ; Yi-Min CHEN ; Zhe-Yao XIE ; Yuan-Qin CAI ; Xi WANG
China Journal of Chinese Materia Medica 2025;50(2):293-300
This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals
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Alzheimer Disease/physiopathology*
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Male
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TOR Serine-Threonine Kinases/genetics*
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Autophagy/drug effects*
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Rats, Sprague-Dawley
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Protein Serine-Threonine Kinases/genetics*
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AMP-Activated Protein Kinases/genetics*
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Rats
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Drugs, Chinese Herbal/administration & dosage*
;
Signal Transduction/drug effects*
;
AMP-Activated Protein Kinase Kinases
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Humans
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Hippocampus/metabolism*
5.Analysis of the incidence and mortality characteristics of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019
Xiaorong CHEN ; Liuxia YAN ; Zheng LONG ; Lei HOU ; Xiaoning CAI ; Limin WANG ; Jing WU
Chinese Journal of Preventive Medicine 2025;59(2):202-208
Objective:To analyze the characteristics and changes in incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019.Methods:The incidence and mortality data of ischemic and hemorrhagic stroke from 2015 to 2019 were collected from the China Registry of Cardiovascular Events (China RACE), which was established in 2014 and covered 100 counties (cities and districts) in 31 provinces in China. The age-standardized incidence rate (ASIR) was calculated using the Seventh National Census data as the standard population. The ratio of the incidence rate of ischemic stroke to hemorrhagic stroke was calculated. The subtype-specific mortality-to-incidence ratio (M/I) was calculated by the ratio of the number of deaths to the reported incidence cases. The relative ratio (RR) of M/I for ischemic to hemorrhagic stroke was calculated. The Joinpoint model was used to analyze the annual percentage change (APC) and trend of the incidence rate of stroke.Results:From 2015 to 2019, a total of 1 354 614 new stroke cases were reported, including 1 077 244 (79.52%) ischemic stroke and 277 370 (20.48%) hemorrhagic stroke cases, respectively. A total of 248 620 stroke deaths were reported, including 119 819 (48.19%) ischemic stroke deaths and 128 801 (51.81%) hemorrhagic stroke deaths. The incidence ratio of ischemic/hemorrhagic stroke from 2015 to 2019 was 3.50∶1, 3.76∶1, 3.63∶1, 4.23∶1, and 4.35∶1, respectively. From 2015 to 2019, there was no statistically significant annual trend of ASIR of ischemic stroke in overall, urban and rural areas and males ( Ptrend>0.05), while there was a downward trend in females (APC=-1.02%, Ptrend=0.042). The incidence of hemorrhagic stroke in the whole population, rural areas, males and females showed a downward trend ( Ptrend<0.05). Patients aged 45-49 years had an upward trend in the incidence rate of ischemic stroke (APC=3.82%, Ptrend=0.011), while those aged 70-74 years (APC=-7.37%, Ptrend=0.034), 80-84 years (APC=-9.75%, Ptrend=0.001) and 85 years and over (APC=-11.22%, Ptrend=0.017) presented a downward trend in the incidence of hemorrhagic stroke. During the period, the overall relative ratio of M/I (RR) for ischemic to hemorrhagic stroke was 4.2∶1, which was lower in urban than in rural areas (3.8 vs. 4.3). The largest gap between urban and rural areas was in the 55-59 age group (6.8 vs. 9.3). Conclusion:The incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents are severe from 2015 to 2019, and there are regional and population differences.
6.Deep learning model based on fundus images for detection of coronary artery disease with mild cognitive impairment
Yi YE ; Wei FENG ; Yao-dong DING ; Qing CHEN ; Yang ZHANG ; Li LIN ; Tong MA ; Bin WANG ; Xian-gang CHANG ; Zong-yuan GE ; Xiao-yi WANG ; Long-jun CAI ; Yong ZENG
Chinese Journal of Interventional Cardiology 2025;33(6):303-311
Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50% stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE<27 or MoCA<26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95%CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95%CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95%CI 0.714-0.802),corresponding to a validated AUC of 0.710(95%CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95%CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95%CI 0.719-0.778)and the specificity was 0.561(95%CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95%CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.
7.Clinical efficacy of 3 surgical methods for spontaneous supratentorial intracerebral hemorrhage
Ping SONG ; Zhiyang LI ; Pan LEI ; Qiuwei HUA ; Lun GAO ; Hongxiang JIANG ; Long ZHOU ; Hui YE ; Qianxue CHEN ; Qiang CAI
Chinese Journal of Neuromedicine 2025;24(2):154-162
Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.
8.Clinical features and prognosis of acute B lymphoblastic leukemia children carrying a TCF3: : PBX1 fusion gene
Lulu HUANG ; Yunyan HE ; Yang LI ; Danna LIN ; Ning LIAO ; Yayun LING ; Lyuhong XU ; Xinyu LI ; Huirong MAI ; Ying WANG ; Wuqing WAN ; Ying LIU ; Yanlai TANG ; Xiaoli ZHANG ; Chuan TIAN ; Xiaofeng LI ; Qiwen CHEN ; Xingjiang LONG ; Liuhua LIAO ; Qiaoru LI ; Jianling CAI ; Zijun ZHEN ; Zhiguang LI ; Keyan YANG ; Qinlong ZHENG ; Lihua YANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(7):497-502
Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.
9.Trends in case fatality of hemorrhagic stroke and ischemic stroke in China, 2015-2019
Xiaorong CHEN ; Jing WU ; Lei HOU ; Xiaoning CAI ; Zheng LONG ; Liuxia YAN ; Limin WANG
Chinese Journal of Epidemiology 2025;46(8):1354-1359
Objective:To present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.
10.Expression characteristics of OPG/RANKL/RANK and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure
Xin YANG ; Xue-kun CAI ; Ze-long WU ; An-tao CHEN ; Zi-hao CHEN ; Xuan XIE ; Jia-kang OU ; Zhao-qi HUANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):71-75
Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)%,(2.40±0.25)%,(3.65±0.25)%,(5.43±0.29)%,(6.97±0.36)%and(9.38±0.49)%;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P<0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP<0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

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