1.Buzhong Yiqitang Regulates Endoplasmic Reticulum Stress to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer via Nrf2/ROS Pathway
Dan YU ; Qirui MU ; He LI ; Yuetong LIU ; Jingyi HUANG ; Yuan GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):98-104
ObjectiveTo investigate the mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer by observing the effects of Buzhong Yiqitang on endoplasmic reticulum stress-related molecules in human lung adenocarcinoma cells (A549) and cisplatin-resistant cells in human lung adenocarcinoma cells (A549/DDP) via the nuclear factor E2-related factor 2(Nrf2)/reactive oxygen species(ROS) pathway. MethodsThe serum containing Buzhong Yiqitang was prepared and A549 cells and A549/DDP cells were cultured. The cells were randomized into groups A (A549 cells+blank serum), B (A549 cells+20 mg·L-1 cisplatin+blank serum), C (A549 cells+20 mg·L-1 cisplatin+10% Buzhong Yiqitang-containing serum), D (A549/DDP cells+blank serum), E (A549/DDP cells+20 mg·L-1 cisplatin+blank serum), and F (A549/DDP cells+20 mg·L-1 cisplatin+10% Buzhong Yiqitang-containing serum). The cell counting kit-8 (CCK-8) method was used to detect the half maximal inhibitory concentration (IC50) of cisplatin. The protein levels of Nrf2 and p-Nrf2 were determined by Western blotting. The DCFH-DA fluorescent probe was used to measure the content of reactive oxygen species (ROS) in each group. The protein levels of glucose-regulated protein 78 (GRP78), activated transcription factor 6 (ATF6), and C/EBP-homologous protein (CHOP) were determined by Western blot. ResultsCompared with group B, group C showed a reduction in IC50 of cisplatin (P<0.05), which held true in group E compared with group F (P<0.05). Moreover, the IC50 of cisplatin to A549/DDP cells was higher than that to A549 cells before and after Buzhong Yiqitang intervention (P<0.05). Compared with group A, group B showed up-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05). Compared with group B, group C showed down-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05). Compared with group D, group E showed up-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05), which, however, were significantly down-regulated in group F (P<0.05). The ROS content and the protein levels of GRP78, ATF6, and CHOP followed a descending trend of group C > group B > group A in A549 cells and group F > group E > group D in A549/DDP cells (P<0.05). Moreover, the ROS content and the protein levels of GRP78, ATF6, and CHOP in A549 cells were higher than those in A549/DDP cells before and after Buzhong Yiqitang intervention (P<0.05). ConclusionBuzhong Yiqitang may regulate endoplasmic reticulum stress via the Nrf2/ROS pathway to attenuate cisplatin resistance in non-small cell lung cancer.
2.Effect of MOTS-c on hepatocyte injury induced by glycochenodeoxycholic acid by regulating transporter MRP2 expression
Yu AO ; Xuyang ZHANG ; Dan TANG ; Gongwei LIU ; Dan HUANG ; Zhifang CAI
Organ Transplantation 2025;16(3):425-434
Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.
3.EGCG Promotes Aβ Clearance of Microglia Through Blockage of the HDAC6-PI3K/AKT/mTOR Signalling Axis Followed by Autophagy Activation
Yu LIN ; Kaiwen HUANG ; Honghai HONG ; Dan ZHU ; Yousheng MO ; Dongli LI ; Shuhuan FANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):486-497
ObjectiveTo clarify whether epigallocatechin gallate (EGCG) is involved in the clearance of amyloid β-protein (Aβ) and autophagy induction by microglia, so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease (AD). MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups, with some additional wild type (WT) mice as the control group, each group consisting of 15 mice. The EGCG group received continuous gavage administration[5 mg/(kg·d)] for 8 weeks, followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein (Aβ)in the brain parenchyma of the mice, and immunofluorescence was employed to detect the expression levels of Aβ1-42, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the hippocampal tissue of the mice. Additionally, N9 mouse microglial cells were induced with 20 µmol/L Aβ1-42, and the cell viability was measured after treatment with different concentrations of EGCG (5 µmol/L, 10 µmol/L, 20 µmol/L). Western blotting was used to detect the levels of Aβ1-42, low density lipoprotein receptor-related protein 1(LRP1), receptor for advanced glycation endproducts (RAGE), amyloid precursor protein (APP), insulin degrading enzyme (IDE), neprilysin (NEP), microtubule associated protein 1 hydrogen chain 3(LC3)-Ⅱ/LC3-Ⅰ, phosphatidylinositol 3-hydroxy kinase(PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and histone deacetylase 6(HDAC6). Finally, through the co-culture of microglial cells and neuronal SH-SY5Y cells, cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field (P<0.05), and enhanced the percentage of alternation in the Y-maze test (P<0.01); EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia; in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells (P<0.01), upregulated RAGE activity (P<0.05), and promoted the internalization and phagocytosis of Aβ (P<0.01). ECGC activated microglial autophagy by downregulating the level of HDAC6 (P<0.05), inhibiting the phosphorylation of PI3K, AKT, mTOR (P<0.001), and increasing the LC3-Ⅱ/LC3-I ratio (P<0.001); EGCG improved the survival rate of SH-SY5Y cells (P<0.05) and reduced the activity of Caspase-3 (P<0.01) by clearing Aβ1-42 through microglia, and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.
4.Correlation between myopia progression and visual performance in children
Lu YU ; Tingnan HUANG ; Yimeng QU ; Pei CHEN ; Ying WANG ; Dan LYU ; Liqin ZHOU ; Zheng WANG
International Eye Science 2024;24(5):778-783
The incidence of myopia among Chinese adolescents is progressively rising, indicating a distinct trend toward younger age onset.This paper aims to comprehensively review the impact of various visual performance on myopia and its progression, with a specific emphasis on accommodative function, convergence function, and ocular position. A meticulous exploration of accommodation function, encompassing accommodative amplitude, accommodative facility, accommodative response, positive relative accommodation, and negative relative accommodation, has been undertaken to elucidate its contributory role in myopia progression. Concurrently, an exhaustive analysis of convergence function has been conducted including esotropia and exotropia, convergence insufficiency and convergence excess, fusional function vergence, divergence insufficiency, and excess, providing a nuanced understanding of convergence's implications for myopia advancement. Furthermore, the influence of ocular position on myopia progression, along with other factors affecting perceptual ocular position and intermittent exotropia, is discussed. The primary objective of this article is to unveil the multifaceted visual performance influencing myopia and its progression, elucidating the paramount significance of accommodative function, convergence function, and ocular position in this context.
5.The Role and Possible Mechanisms of Exercise in Combating Osteoporosis by Modulating The Bone Autophagy Pathway
Xin-Yu DAI ; Bin LI ; Dan JIN ; Xue-Jie YI ; Rui-Qi HUANG ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(7):1589-1603
Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.
6.Herbal Textual Research on Curculiginis Rhizoma in Famous Classical Formulas
Jinfang LUO ; Yaoyao HUANG ; Tao ZHOU ; Yang YU ; Guoqiong CAO ; Dan ZHAO ; Chenhong XIAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):199-208
By consulting the ancient and modern literature, the name, origin, quality evaluation, harvesting and processing methods of Curculiginis Rhizoma(CR) were systematically combed and verified, in order to provide a basis for the development and utilization of famous classical formulas containing CR. The results of herbal textual research showed that the name Xianmao was first recorded in Leigong Paozhilun, the name of CR was used in all dynasties and this name came from its efficacy and morphological characteristics, the mainstream source for CR of the past dynasties was the rhizome of Curculigo orchioides or C. capitulata, since modern times, C. orchioides has been the main source of commodities. In ancient times, most of the places of origin of the description were the western regions and southwest China, while in modern times, Sichuan and Guizhou were regarded as genuine places. Since modern times, its quality has been summarized as the best with thick roots, firm texture and black-brown surface, the harvesting and processing methods recorded in the past dynasties are mainly sun drying after harvest in the second, eighth and ninth months of the lunar calendar, and most of them are harvested in autumn and winter in modern times. In ancient times, there were many processing methods of CR, mainly in processing with rice swill, while in modern times, stir-frying with wine was the main processing method. The nature, taste, meridian tropism, functions and indications of CR are basically consistent from ancient to modern times, the taboos for taking are to avoid iron, cow's milk, and beef. Although there are some differences in the understanding of the toxicity of CR in the past dynasties, most of the materia medica are clear that it has a certain toxicity. Based on the research conclusion, it is suggested that the rhizome of C. orchioides of Lycoris family should be used as its source in the famous classical formulas, and the corresponding processing method should be selected according to the processing requirements in the formulas, while the raw products is recommended to be selected as medicine if the processing requirement is not specified.
7.Analysis on clinical characteristics of primary Sj?gren's syndrome complicating atherosclerosis
Wanmei NA ; Yu HUANG ; Hao ZHAO ; Dan WANG
Chongqing Medicine 2024;53(11):1616-1620
Objective To investigate the clinical characteristics of primary Sj?gren's syndrome (pSS) complicating atherosclerosis(AS).Methods The clinical data of the patients with PSS in the rheumatology department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai Univer-sity of Traditional Chinese Medicine from January 2019 to January 2022 were retrospectively analyzed.The pa-tients were divided into the complication group (n=108) and non-complicating group (n=106) according to whether or not complicating AS.The differences in the general data,laboratory indicators and carotid intima-media thickness (IMT) were compared between the two groups.The risk factors were analyzed.Results Compared with the non-complicating group,the age in the complicating group was bigger[66.00(61.25,69.00)years old vs. 59.00(50.75,65.25)years old],the disease course was longer[128.00(108.25,141.75)months vs. 94.00 (74.75,112.25)months],the levels of ESR,monocyte count,interleukin-6 (IL-6),interleukin-2 receptor (IL-2R),total cholesterol and low density lipoprotein-cholesterol were higher[27.00(14.10,48.00)mm/h vs. 22.00(12.00,36.50)mm/h;0.40(0.30,0.50)×109/L vs. 0.30(0.30,0.50)×109/L;3.56(2.17,5.95)pg/mL vs. 2.62(1.00,5.15)pg/mL;519.00(403.00,662.00)U/mL vs. 441.00(348.00,592.00)U/mL;(4.86±1.17)mmol/L vs. (4.55±1.10)mmol/L;(3.07±0.80)mmol/L vs. (2.82±0.78)mmol/L],IMT was larger[left side:0.80(0.80,0.90)mm vs. 0.80(0.78,0.80)mm;right side:0.80(0.80,0.90)mm vs. 0.80 (0.80,0.80)mm],and the differences were statistically significant (P<0.05).The multivariate logistic re-gression analysis results showed that the long disease course (OR=1.080) and ERS level increase (OR=1.021) were the independent risk factors of AS occurrence in pSS (P<0.05).Conclusion There are differ-ences in the serologic indicators between the pSS patients with complicating AS and the pSS patients without complicating AS,and the disease course and ESR level have the influence on it.
8.Systemic inflammatory response index, systemic immune-inflammatory index, and CT perfusion imaging parameters predict early neurological deterioration in patients with minor stroke due to anterior circulation large vessel occlusion
Hu HUANG ; Zhiwei LIU ; Zihan YU ; Chunjie SONG ; Dan LI ; Yuanyuan HAN
International Journal of Cerebrovascular Diseases 2024;32(6):407-413
Objective:To investigate the predictive value of systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and CT perfusion imaging (CTP) parameters for early neurological deterioration (END) in patients with mild stroke duo to anterior circulation large vessel occlusion.Methods:Patients with minor stroke duo to anterior circulation large vessel occlusion admitted to the First People's Hospital of Suqian from November 2021 to December 2023 were included. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5, and END was defined as an increase of ≥ 4 in NIHSS score within 24 hours of admission compared to the baseline. SIRI and SII were calculated based on the findings of blood routine examination. According to CTP at admission, the cerebral blood volume (CBV) index, infarct core volume, and early infarct growth rate (EIGR) were obtained. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each predictor on END. Results:A total of 132 patients were included, with 85 males (64.4%) and a median age of 68 years (interquartile range, 58-77 years). Thirty-nine patients (29.5%) experienced END. The baseline NIHSS score, fasting blood glucose, neutrophil count, lymphocyte count, SIRI, SII, infarct core volume, and EIGR in the END group were significantly higher than those in the non-END group, while the CBV index was significantly lower than that in the non-END group (all P<0.05). Multivariate logistic regression analysis showed that SIRI (odds ratio [ OR] 3.672, 95% confidence interval[ CI] 1.838-6.326; P<0.001), SII ( OR 4.824, 95% CI 2.057-7.135; P<0.001), CBV index ( OR 0.968, 95% CI 0.947-0.986; P<0.001), and EIGR ( OR 2.527, 95% CI 1.918-3.589; P<0.001) were the independent predictive factors of END. ROC curve analysis showed that the area under the curves of SIRI, SII, CBV index, and EIGR for predicting END were 0.780 (95% CI 0.692-0.863), 0.798 (95% CI 0.709-0.888), 0.775 (95% CI 0.697-0.853), and 0.772 (95% CI 0.732-0.829), respectively. Conclusion:SIRI, SII, CBV index, and EIGR are the independent predictive factors of END in patients with minor stroke duo to anterior circulation large vessel occlusion, and have certain predictive value for END.
9.Combined application of auditory brainstem response and auditory steady-state response in the evaluation of infants with mild sensorineural hearing loss
Qiuya JIANG ; Qiuying XIE ; Yu HUANG ; Chao HUANG ; Hongli LAN ; Maojie LIU ; Dan LAI
The Journal of Practical Medicine 2024;40(16):2305-2310
Objective To investigate the significance of auditory brainstem response(ABR)combined with auditory steady-state response(ASSR)for the assessment of mild sensorineural hearing loss in infants.Methods Data from 114 infants with mild sensorineural hearing loss were retrospectively analyzed,and their ABR and ASSR results were collected for rank sum test and correlation analysis.Results In the rank sum test,the difference in thresholds between tone-burst ABR(Tb-ABR)and ASSR at 0.5,1,2,4 kHz was statistically significant(P<0.05),and they were also correlated at 0.5,1,2,4 kHz(P<0.05),r=0.613,0.569,0.616,0.71.After grouping by gender and ear,there was a correlation between ABR and ASSR at 0.5,1,2,and 4 kHz,male:r=0.61,0.56,0.671,0.774;female:r=0.581,0.558,0.546,0.608;left ear:r=0.61,0.558,0.576,0.715;right ear:r=0.631,0.581,0.662,0.71.And after grouping by age at diagnosis,only infants diagnosed from 7~12 months of age did not correlate at 0.5 kHz and 1 kHz(P>0.05),while the rest of the groups had a good correlation(P<0.05),0~3 months:r=0.686,0.643,0.671,0.742;4~6 months:r=0.671,0.626,0.616,0.693;7~12 months at 2 kHz and 4 kHz:r=0.571,0.706.Conclusion In infants with mild sensorineural hearing loss,ABR and ASSR correlate in assessing hearing thresholds at all frequencies,and the combination of the two tests could provide a more accurate assessment of the subject's true hearing.
10.Correlation between Serum miR-122 and miR-558 Levels and Cardiac Function and Heart Rate Variability in Patients with Chronic Heart Failure
Yan LIN ; Hanliang DAN ; Yang YU ; Peng GAO ; Jiliang HUANG ; Yang BAI
Journal of Modern Laboratory Medicine 2024;39(3):37-41,114
Objective To explore the relationship between serum microRNA(miR)-122 and microRNA(miR)-558 levels and cardiac function and heart rate variability in patients with chronic heart failure(CHF).Methods A total of 100 patients with chronic heart failure who were hospitalized in Wuhan Dongxihu District Poeple's Hospital from January 2019 to January 2022 were regarded as the study group,and 100 healthy individuals who underwent physical examinations in the hospital during the same period served as the control group.The real-time fluorescence quantitative PCR method was applied to detect the expressiou levels of serum miR-122 and miR-558 in two groups.The heart rate variability and cardiac function indicators of the two groups were compared.Pearson method was applied to analyze the correlation between serum miR-122 and miR-558 expression levels,and heart rate variability and cardiac function indicators in patients with chronic heart failure.Logistic regression was applied to analyze the risk factors affecting chronic heart failure.Results Compared with the control group,the serum miR-122(0.86±0.19 vs 1.07±0.16),heart rate variability indicators,and left ventricular ejection fraction(LVEF)of patients with chronic heart failure were decreased(t=3.844~15.448),and the expression level of miR-558(1.28±0.27 vs 1.02±0.12)and left ventricular end diastolic volume index(LVEDVI),left ventricular end systolic volume index(LVESVI)were increased(t=6.794~9.358),and the differences were statistically significant(all P<0.05).The expression level of serum miR-122(1.19±0.23,1.04±0.21)in patients with functional grades Ⅰ to Ⅱ was higher than that in patients with grades Ⅲ to Ⅳ(0.68±0.16,0.53±0.15),while the expression level of miR-558(0.93±0.24,1.21±0.26)was lower than that in patients with grade Ⅲ-Ⅳ(1.42±0.27,1.64±0.29),with significant differences(qmiR-122=3.751~14.568,qmiR-558=3.929~11.194.all P<0.05).The serum miR-122 level in patients with chronic heart failure was positively correlated with heart rate variability indicators and LVEF(r=0.337~0.573),but negatively correlated with LVEDVI and LVESVI(r=-0.385,-0.323).Serum miR-558 was negatively correlated with heart rate variability indicators and LVEF(r=-0.646~-0.246),but positively correlated with LVEDVI and LVESVI(r=0.528,0.547).Serum miR-122[OR(95%CI)=0.528(0.328~0.850)]and miR-558[OR(95%CI)=2.845(1.364~5.933)]were influencing factors for chronic heart failure(P<0.05).Conclusion The expression levels of serum miR-122 and miR-558 in patients with chronic heart failure were closely related to heart rate variability and cardiac function,indicating that serum miR-122 and miR-558 may be influencing factors of chronic heart failure.

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