1.Effect of Influenza A Virus on BEAS-2B in Human Lung Epithelial Cells and Intervention Effect of Shufeng Jiedu Capsule-containing Serum
Shan CAO ; Zihan GENG ; Lei BAO ; Yingli XU ; Bo PANG ; Jingsheng ZHANG ; Yu ZHANG ; Mengping CHEN ; Yaxin WANG ; Ronghua ZHAO ; Shanshan GUO ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):90-97
ObjectiveTo observe the effect of Shufeng Jiedu capsule (SFJD)-containing serum on human lung epithelial cells infected by influenza A virus, and investigate the protective effect of the drug on the cells and the potential antiviral effect. MethodThe SFJD-containing serum was prepared and used to treat human lung epithelial cells (BEAS-2B) cultured in vitro. The viability of cells treated with different concentrations of SFJD-containing serum was measured by the cell counting kit-8 (CCK-8), and the optimal concentration of SFJD-containing serum was screened for subsequent experiments. BEAS-2B cells were classified into normal control, virus infection, and SFJD-containing serum groups, and the CCK-8 method was used to detect the survival rate of BEAS-2B cells after virus infection and drug administration. The expression of influenza virus nucleic acid in the cells of each group was determined, and the apoptosis of cells in different groups was observed by fluorescence microscopy. Real-time PCR was employed to determine the mRNA levels of influenza virus nucleoprotein (NP), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88) in each group of cells. The immunofluorescence assay was used to detect the fluorescence intensities of TLR4, MyD88, and phosphorylated nuclear factor-κB (p-NF-κB) in lung epithelial cells. ResultCompared with that in the control group (normal serum), the cell survival rates in the blank serum and the SFJD-containing serum (5%, 10%, and 20%) groups were 100.00%±0.00%, 89.05%±4.80%, 87.13%±5.90%, 93.83%±6.03%, and 99.33%±3.39%, respectively (P<0.01). The SFJD-containing serum of 20% was selected as the optimal treatment for subsequent experiments. Compared with the normal control group, the virus infection group showed reduced cell survival rate (P<0.01), and the reduction was increased by the SFJD-containing serum (P<0.01). Compared with the virus infection group, SFJD-containing serum reduced the virus load (P<0.01) to decrease apoptosis. Compared with the normal control group, the virus infection group showed up-regulated mRNA levels of NP, TLR4, and MyD88 (P<0.01), and the up-regulation was down-regulated by the SFJD-containing serum (P<0.05, P<0.01). The fluorescence intensities of TLR4, MyD88, and p-NF-κB proteins in the cells increased after virus infection compared with those in the normal control (P<0.05, P<0.01), and they were decreased after administration with the SFJD-containing serum (P<0.05). ConclusionThe SFJD-containing serum can inhibit influenza virus in vitro by increasing the survival rate, reducing the apoptosis, and down-regulating the protein levels of TLR4, MyD88, and p-NF-κB in BEAS-2B cells.
2.Efficacy and Mechanism of Lutongning Granules in Treatment of Trigeminal Neuralgia Induced by Injection of Talc into Infraorbital Foramen of Model Rats Based on P2X7R-mediated Neuroinflammation
Qiyue SUN ; Shuran LI ; Shuangrong GAO ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Jingsheng ZHANG ; Bo PANG ; Yingli XU ; Yu ZHANG ; Shan CAO ; Yaxin WANG ; Xiaolan CUI ; Bing HAN ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):56-63
ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
3.Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease
Ying SUN ; Bin WANG ; Yuefeng YU ; Yuying WANG ; Xiao TAN ; Jihui ZHANG ; Lu QI ; Yingli LU ; Ningjian WANG
Chinese Medical Journal 2024;137(10):1160-1168
Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.
4.Life’s Essential 8 and risk of non-communicable chronic diseases: Outcome-wide analyses
Yuetian YU ; Ying SUN ; Yuefeng YU ; Yuying WANG ; Chi CHEN ; Xiao TAN ; Yingli LU ; Ningjian WANG
Chinese Medical Journal 2024;137(13):1553-1562
Background::Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.Methods::In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.Results::During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).Conclusions::Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.
5.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
6.Current Status of Self-transcendence among Lung Cancer Patients and Its Influencing Factors
YANG XUE ; LUO YU ; YE LIJUAN ; YU YINGLI ; ZHU DAXING
Chinese Journal of Lung Cancer 2024;27(7):523-528
Background and objective Different degrees of self-transcendence exist in lung cancer patients,which can stimulate patients'self-awareness and promote them to face negative events in life positively,thus improving pa-tients'quality of life and treatment outcomes.However,there are few reports on self-transcendence in lung cancer patients in China,and the related influencing factors have not yet been clarified.This study aims to investigate the current situation of self-transcendence in lung cancer patients and explore its risk factors,so as to provide a theoretical basis for clinical intervention decision-making.Methods 243 lung cancer patients who were admitted to the Department of Lung Cancer Center of West China Hospital,Sichuan University from September 2023 to February 2024 were enrolled as the study subjects;general infor-mation questionnaire,self-transcendence scale,Herth hope scale and social support scale were used for the investigation.The influencing factors related to self-transcendence of lung cancer patients were analyzed.Results The total mean score of self-transcendence in lung cancer patients was(44.73±8.94);the total mean score of hope level was(37.60±4.98),and the total mean score of social support was(41.31±7.27).Self-transcendence was positively correlated with hope level and social support(P<0.001,P<0.001).Education,hope level and social support were influencing factors of self-transcendence in lung cancer pa-tients(P<0.05,P<0.001,P<0.05).Conclusion Self-transcendence in lung cancer patients was at a low level and was influenced by hope level and social support.Healthcare professionals should pay attention to improving the hope level of lung cancer pa-tients,carrying out targeted psychological interventions,and at the same time guiding them to enhance the perception of social support,so as to promote the realization of self-transcendence in patients.
7.Effect of motor acupuncture based on movement pattern adjustment theory in the treatment of non-specific low back pain
Yingli YU ; Yuandong CHENG ; Yuanqin MOU ; Yuqin WANG ; Liugang TANG ; Tai LIU
Journal of Clinical Medicine in Practice 2024;28(21):100-104
Objective To explore the effects of motor acupuncture based on movement pattern adjustment theory on Oswestry Disability Index (ODI), modified Japanese Orthopedic Association (JOA) score and the prognosis in patients with non-specific low back pain (NLBP). Methods A total of 98 patients with NLBP who were admitted to the hospital from March 2020 to March 2023 were randomly divided into control group and observation group, with 49 patients in each group. The control group received lumbar and pelvic rhythm training, while the observation group received motor acupuncture based on movement pattern adjustment theory. The Visual Analogue Scale (VAS) score, ODI score, JOA score, low back electromyographic signals[the ratio of maximum EMG during extension to maximum EMG during maximum voluntary flexion (EXT/MVF) and the ratio of maximum EMG during flexion to maximum EMG during maximum voluntary flexion (FLEX/MVF)], and serum inflammatory factors[interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α] in both groups were observed before and after treatment. Clinical efficacy and 3-month recurrence rate were compared between the two groups. Results After 2 weeks of treatment, VAS score and ODI score of the observation group were lower than those of the control group, and JOA score was higher than that of the control group (
8.Recent advance in role of nicotinamide mononucleotide in central nervous system diseases
Chunjia ZHANG ; Yan LI ; Yan YU ; Fan BAI ; Yingli JING ; Degang YANG ; Feng GAO ; Jianjun LI
Chinese Journal of Neuromedicine 2023;22(9):947-952
Nicotinamide mononucleotide (NMN) is an important precursor in conversing nicotinamide adenine dinucleotide (NAD +) in the body. By elevating NAD + level in the body, NMN enhances the hydrogen transfer function of NAD + in biological processes, promotes the synthesis of proteins and polysaccharides, improves substance transportation and regulatory efficiency, and enhances metabolic functions. Specifically, in central nervous system disease, NMN exerts neuroprotective effect through antioxidation, anti-inflammation, mitochondrial protection, and prevention of neuronal and axonal degeneration. This review focuses on the therapeutic role of NMN in common central nervous system diseases and their neuroprotective mechanisms, so as to further understand the role of NMN in central nervous system diseases, and provide references for predicting therapeutic targets and screening therapeutic drugs for central nervous system diseases.
9.Transcriptomic analyses in hippocampus based on RNA-seq and construction of a competing endogenous RNA regulatory network in mice with sepsis-associated encephalopathy
Yingli ZHANG ; Mingdong YU ; Chenglin LIU ; Pei LI ; Huixing WANG ; Jing ZHANG ; Liguo WEI ; Yonghao YU ; Keliang XIE ; Yuechun LU
Chinese Journal of Anesthesiology 2023;43(9):1117-1123
Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.
10.Effect of dexmedetomidine on expression of DNA methyltransferases in septic mice with acute lung injury
Pei LI ; Mingdong YU ; Yingli ZHANG ; Chenglin LIU ; Wanlu REN ; Jianbo YU
Chinese Journal of Anesthesiology 2023;43(12):1510-1514
Objective:To evaluate the effect of dexmedetomidine on the expression of DNA methyltransferases in septic mice with acute lung injury.Methods:Forty-eight clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation + dexmedetomidine group(group Sham+ DEX), sepsis group (group Sepsis) and sepsis + dexmedetomidine group(group Sepsis+ DEX). Sepsis model was established by cecal ligation and puncture(CLP)in anesthetized mice. At 30 min before model preparation, dexmedetomidine 0.05 μg/g (in 0.5 ml of normal saline) was administered in Sham + DEX and Sepsis + DEX groups, and normal saline 0.5 ml was given instead in Sham and Sepsis groups. The mice were sacrificed at 24 h after CLP, and the lung tissue was taken to determine the wet to dry lung weight ratio, contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and high mobility group box-1 (HMGB-1), activities of superoxide dismutase (SOD) and myeloperoxidase (MPO), and content of malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), global DNA methylation (by colorimetric assay), and expression of DNA methyltransferases (DNMTl, DNMT3a, DNMT3b) (by Western blot) and to examine the histopathological changes of lung tissues (by HE staining) which were scored. Results:Compared with group Sham, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly increased, SOD activity was decreased, and the expression of DNMT1 and DNMT3a was up-regulated in group Sepsis and group Sepsis+ DEX ( P<0.05), and no significant change was found in the aforementioned indexes in group Sham+ DEX ( P>0.05). Compared with group Sepsis, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly decreased, SOD activity was increased, and the expression of DNMT1 and DNMT3a was down-regulated in group Sepsis+ DEX ( P<0.05). Conclusions:The mechanism by which dexmedetomidine reduces acute lung injury is related to inhibition of up-regulation of DNMT1 and DNMT3a expression in septic mice.


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