1.The alteration of energy metabolism and oxidative injury in the myocardia suffering from lethal ventricular ;tachyarrhythmia (
Zongtai ZHENG ; Wenfang CHEN ; Jiaquan WENG ; Nanwei ZHANG ; Zhiwei SHEN ; Jiayan WU ; Xingxing WANG ; Dian WANG
Chinese Journal of Forensic Medicine 2016;31(6):543-546,549
Objective To investigate the alteration of energy metabolism and oxidative injury in the myocardia suffering from lethal ventricular tachyarrhythmia (LVTA). Methods Two LVTA-SCD SD rat models, induced by aconitine injection or coronary artery ligation (CAL), respectively, were developed. Rats that died from over-anaesthesia or CAL-induced heart failure were served as their controls, respectively. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS), malonaldehyde (MDA), phosphocreatine (PCr) in the ventricular myocardia, and serum troponin I (cTnI) were detected, and compared between LVTA rats and their controls. Results Fourteen ACO-LVTA and six CAL-LVTA rats were successfully developed. As compared to their controls, ACO-LVTA and CAL-LVTA rats had higher ROS and MDA content, and lower concentration of PCr in the ventricular myocardia. MDA content in ACO-LVTA group is signiifcantly higher than that of its control (P<0.05). MMP in myocardia of ACO-LVTA is lower than that of its control, but is higher than those of two CAL groups. Serum cTnI in rats of both LVTA models is higher than those of their controls and pre-treated control. Specially, serum cTnI in CAL-LVTA was signiifcantly higher than that of ACO-LVTA and its control (P<0.01). The myocardial ROS content is correlated with the duration of VT and VF (P<0.05), with correlation coefifcients being 0.44 and 0.46, respectively. Conclusions After LVTA, the ventricular myocardia had lower MMP and PCr content, higher concentration of ROS, MDA, as well as higher serum cTnI than their controls, indicative of oxidative injury and alteration of energy metabolism under LVTA-SCD.
2.Experimental study on liver ischemia reperfusion injury promoted by NOD1 activated pyroptosis
Jiri XI ; Hu SONG ; Xingxing WANG ; Shipeng LI ; Shuang YANG ; Jinzhen CAI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2019;40(1):41-45
Objective To investigate the effect of nucleotide-binding oligomerization domaincontaining protein 1 (NOD1) on pyroptosis in hepatic ischemia-reperfusion injury.Methods An animal model of ischemia-reperfusion injury was established.Thirty healthy,male,and clean C57 BL mice were randomly divided into sham operation group (sham group) and ischemia-reperfusion group (IR,including 2 h,6 h,12 h,24 h subgroups),6 per group.Serum ALT and AST levels in each group were measured by blood biochemistry.HE staining and TUNEL were used to observe the pathological changes of liver and hepatocyte apoptosis.Immunohistochemistry was used to detect the expression and distribution of NOD1 in each group.Western blotting was used to detect NOD1,MM2,pro-Caspase-1 and active-Caspase-1 expression.NOD1 siRNA and empty control siRNA were transfected into AML12 cells,then the hypoxia/reoxygenation model was established and cells were collected to detect the expression of NOD1,AIM2 and active-Caspase-1.Results The ALT and AST levels in IR group were significantly higher than those in sham group,and peaked at IR 12-h subgroup (P<0.05).HE staining showed that hepatic injury was the most severe at 12 h after reperfusion.TUNEL results showed that the number of apoptotic cells was the greated at 12 h after reperfusion.Western blotting showed that NOD1 protein expression was highest at 12 h after reperfusion.With the prolongation of reperfusion time,the expression of AIM2 and active-Caspase-1 gradually increased,and that of pro-Caspase-1 gradually decreased.The expression of NOD1,AIM2 and activeCaspase-1 decreased after transfection of NOD1 siRNA into AML12 cells.Conclusions NOD1 promotes liver ischemia-reperfusion injury,which may be related to NOD1 promoting liver injury by activating pyroptosis.
3.A survey study on major surgeon′s mental trauma caused by iatrogenic biliary injury during laparoscopic cholecystectomy
Kaicheng SHEN ; Tian YANG ; Haisu DAI ; Xingxing SU ; Yishi YANG ; Chengcheng ZHANG ; Ping BIE ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2020;19(5):511-518
Objective:To conduct a survey on major surgeon′s mental trauma caused by iatrogenic biliary injury (IBI) during laparoscopic cholecystectomy (LC), and explore its influencing factors.Methods:The retrospective cross-sectional survey was conducted. Surgeons who have registered in Chinese College of Surgeons of Chinese Medical Doctor Association and Chinese Surgical Society of Chinese Medical Association were recruited to participate as respondents between December 1, 2018 and January 1, 2019. The survey was conducted by the questionnaires of influencing factors for surgeon′s mental trauma caused by IBI during LC. The questionnaires were distributed to participants via WeChat on the Wenjuanxin platform. Observation indicators: (1) results of questionnaire survey; (2) analysis of influencing factors for severe mental trauma of major surgeons caused by IBI during LC. Measurement data with normal distribution were expressed as Mean± SD, and count data were expressed as absolute numbers or percentages. The chi-square test was used for univariate analysis. Factors with P<0.10 in the univariate analysis were included in multivariate analysis, and Logistic regression model was used for multivariate analysis. Results:(1) Results of questionnaire survey. A total of 606 questionnaires were retrieved. ① Basic information of major surgeons: of the 606 major surgeons, there were 596 males and 10 females, aged (41±7)years, with a range from 18 to 62 years. Of the 606 major surgeons, 59.24%(359/606) came from non-teaching hospitals, and 64.03%(388/606) encounted the most impressive case of IBI during LC when they were in the primary or intermediate professional title. For 76.24%(462/606) of the major surgeons, the first case of IBI during LC was the most impressive case, and 69.80%(423/606) believed that careful operation during LC could avoid IBI. ② Patient information: of the patients with the most impressive IBI during LC in each major surgeon′s memory, there were 400 females and 206 males. The proportion of patients younger than 35 years old, in 35-65 years old and older than 65 years old was 9.57%(58/606), 65.51%(397/606), and 24.92%(151/606), respectively. ③ IBI related information: 57.43%(348/606) of the major surgeons indicated that they could receive help from senior surgeons in time for the occurrence of IBI during LC, and 78.88%(478/606) of the major surgeons invited senior surgeons to participate in the initial repair. For the most impressive case of IBI during LC, 66.83%(405/606) of the primary repair surgeries were performed during LC, 11.06%(67/606) were performed within postoperative 3 days and 22.11%(134/606) were performed after 3 days. The main repair methods included local repair, bile duct to end anastomosis, and bilioenteric anastomosis, accounting for 24.92%(151/606), 30.20%(183/606), 33.17%(201/606), respectively. The proportion of patients requiring partial hepatectomy, with perioperative death, and requiring multiple repair was 2.48%(15/606), 2.15%(13/606), and 9.24%(56/606), respectively. ④ Subsequent processing on major surgeons: after the occurrence of IBI during LC, 64.85%(393/606) of the major surgeons gained the understanding of patients and their families, 35.15%(213/606) of the major surgeons were involved in medical disputes, 15.68%(95/606) of the major surgeons received administrative punishment from the hospital. About the compensation, 14.36%(87/606) of the major surgeons had to pay for the compensation by themselves, and only 6.77%(41/606) of the major surgeons had medical liability insurance. There were 9.24%(56/606) of the major surgeons invloved in violent conflicts during the medical disputes. ⑤ Psychology-related information of major surgeons: of the 606 major surgeons, 544 had mental trauma including 279 with severe mental trauma. After the occurrence of IBI during LC, 82.01%(497/606) of the major surgeons experienced anxiety and/or depression for more than one month; 63.37%(384/606) of the major surgeons expected to avoid LC or showed tension during LC; 44.72%(271/606) of the major surgeons had a physiological response when recalling the case; 36.14%(219/606) of the major surgeons initiated the idea of not being a surgeon; 6.44%(39/606) of the major surgeons asked psychologists for help; and 5.61%(34/606) of the major surgeons had taken psychiatric drugs such as antianxiety and anti-depression drugs for more than one month. (2) Analysis of influencing factors for severe mental trauma of major surgeons caused by IBI during LC. Results of univariate analysis showed that the hospital type of the major surgeons, participation of senior surgeons in the repair, surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administrative punishment from the hospital, compensation paid by the major surgeon, having medical liability insurance, violent conflicts in medical disputes were related factors for severe mental trauma of the major surgeons caused by IBI during LC ( χ2=7.688, 3.932, 19.764, 13.837, 61.488, 24.904, 30.976, 5.344, 26.285, P<0.05) . Results of multivariate analysis showed that the surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administrative punishment from the hospital, compensation paid by the major surgeon, violent conflicts in medical disputes were independent risk factors for severe mental trauma caused by IBI during LC of the major surgeons ( odds ratios=1.203, 2.198, 2.922, 1.830, 2.405, 2.171, 95% confidence interval: 1.033-1.402, 1.143-4.226, 1.944-4.391, 1.083-3.093, 1.076-5.375, 1.002-4.702, P<0.05). Having medical liability insurance was an independent protective factor for severe mental trauma of the major surgeons caused by IBI during LC ( odds ratios=0.336, 95% confidence interval: 0.126-0.896, P<0.05). Conclusions:Most surgeons in China are troubled by IBI during LC, and nearly half of them suffer from severe mental trauma. Surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administartive punishment from the hospital, compensation paid by the major surgeon, and violent conflicts in medical disputes are independent risk factors for severe mental trauma of major surgeons caused by IBI during LC. Having medical liability insurance is an independent protective factor for severe mental trauma of major surgeons caused by IBI during LC.
4.Evaluation of right ventricular-pulmonary artery coupling in patients with acute pulmonary embolism by the ratio of tricuspid annular plane systolic excursion and tricuspid regurgitation pressure gradient
Xin DUAN ; Wenqian SHEN ; Shuang WANG ; Shuang CHEN ; Haiyuan YU ; Xingxing REN ; Qiqi LIU ; Zeya SUN ; Guoqing DU
Chinese Journal of Ultrasonography 2021;30(11):982-987
Objective:To evaluate the feasibility of a new ultrasonic parameter to assess right ventricular-pulmonary artery (RV-PA) coupling in patients with acute pulmonary embolism (APE).Methods:A retrospective analysis was performed in 140 patients with APE diagnosed by computed tomography pulmonary angiography (CTPA) in the Second Affiliated Hospital of Harbin Medical University from August 2017 to June 2020. According to the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio cutoff value 0.40 mm/mmHg reported by the European Society of Cardiology in 2020, the patients were divided into the coupling group ( n=99) and the uncoupling group ( n=41). The conventional ultrasonic parameters of the 2 groups were measured, and then several ultrasonic parameter ratios were obtained. The new ultrasonic parameter, which can replace the TAPSE/PASP ratio, was screened out by Spearman correlation analysis, and ROC curve was plotted to calculate the diagnostic efficacy of this parameter. Results:①Compared with the coupling group, patients in the uncoupling group were older and more likely to be accompanied by dyspnea and venous thrombosis in the lower extremities (all P<0.05), but there was no significant difference in other general data(all P>0.05); ②Compared with the coupling group, tricuspid regurgitation velocity (TRV), tricuspid regurgitation pressure gradient(TRPG), PASP, right ventricle end-diastolic transverse diameter(RVTD), inferior vena cava(IVC) diameter and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity(E/e′), in the uncoupling group increased significantly (all P<0.05), and TAPSE, peak systolic velocity of tricuspid annulus(s′), TAPSE/PASP ratio, TAPSE/TRPG ratio, TAPSE/RVTD ratio and s′/TRPG ratio decreased significantly (all P<0.05); ③The TAPSE/TRPG ratio was highly correlated with TAPSE/PASP ratio ( rs=0.970, P<0.001); The TAPSE/TRPG ratio was still highly correlated with TAPSE/PASP ratio in the uncoupling and coupling groups ( rs=0.966, 0.922; all P<0.001). ④ROC analysis showed that the area under curve for TAPSE/TRPG in diagnosing RV-PA coupling was 0.992. At the cutoff of TAPSE/TRPG <0.625 mm/mmHg for indicating RV-PA coupling, the sensitivity and specificity were 97.6% and 92.9%, respectively. Conclusions:TAPSE/TRPG ratio can be used as a new ultrasonic parameter to reflect RV-PA coupling, which is helpful for clinical identification of APE patients with high risk and poor prognosis.
5.Influence of built environment on circulatory disease mortality: A case study of 17 cities in China
Xingxing ZHAI ; Yusheng SHEN ; Shenghui CUI
Journal of Environmental and Occupational Medicine 2022;39(2):161-167
Background In view of circulatory diseases, most previous studies focused on the impacts of air pollution and meteorological factors, while ignoring the influence of built environment. Objective To investigate and quantify the impact of built environment on circulatory diseases in China. Methods Circulatory disease mortality data and built environment data (including urban greenery coverage, urban land use, urban land use mix, urban road facilities and urban medical facilities) of 17 cities in China from 2000 to 2019 were collected. Multiple linear regression was used to analyze which built environment elements had significant influence on circulatory diseases, and to quantify their effects. Furthermore, the changes of built environment indicators on circulatory disease mortality were evaluated under different levels of urban economic development and various air quality. Results The built environment affected the mortality of circulatory diseases during the study period (P<0.05). Urban green space and commercial land area were negatively correlated with circulatory disease mortality, and regression coefficients were −0.550 and −0.280, respectively (P<0.05). On the contrary, the increase of urban road area, residential land ratio, and the degree of land use mix were positively associated with circulatory disease mortality, and their regression coefficients were 0.322, 0.283, and 0.176, respectively (P<0.05). When the level of urban economic development was low, the impact of commercial land use ratio on circulatory diseases was stronger, and the regression coefficient was −0.476 (P<0.05). When urban air pollution worsened, the impacts of per capita green coverage area and per capita urban road area on the disease were more prominent, and the regression coefficients were −0.528 and 0.372, respectively (P<0.05). Conclusion There is a significant correlation between urban built environment and mortality of circulatory diseases. To be specific, circulatory disease mortality has a negative correlation with per capita green coverage area and commercial land use ratio, and a positive correlation with per capita urban road area, residential land ratio and degree of land use mix.
6.Characteristics of paravertebral muscles in patients with unilateral lumbar disc herniation
Xingxing SHEN ; Weijian CHEN ; Congcong LI ; Junyi LI ; Shuai WANG ; Zixuan YE ; Ruian XIANG ; Xuemeng XU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(9):1098-1103
ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.
7.Difference of cervical and shoulder muscle performance and its correlation with pain and body mass index in patients with chronic neck pain
Xingxing SHEN ; Yuling XIONG ; Weijian CHEN ; Congcong LI ; Junyi LI ; Shuai WANG ; Jiahao ZHANG ; Ruian XIANG ; Jiahao CHEN ; Wengang LIU ; Xuemeng XU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(12):1420-1428
ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.
8.Taurine inhibits M2 polarization of macrophages by promoting mitophagy.
Chengying CHEN ; Chunhua LAN ; Jianglang YUAN ; Xingxing KONG ; Li LAN ; Xinhang WANG ; Shengboxiaoji CHANG ; Cailing LU ; Xiyi LI ; Shen TANG
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):488-493
Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy
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Taurine
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Macrophages/metabolism*
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Protein Kinases/metabolism*
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RNA, Messenger
9.Reliability on evaluation of quadriceps femoris muscle quality by ultrasonic echo intensity in patients with knee osteoarthritis
Junyi LI ; Zehua CHEN ; Zugui WU ; Yi WANG ; Congcong LI ; Shuai WANG ; Weijian CHEN ; Zixuan YE ; Xingxing SHEN ; Ruian XIANG ; Wengang LIU ; Xuemeng XU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(6):738-744
ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.
10.A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6.
Liping LIAO ; Wenzhen DANG ; Tingting LIN ; Jinghua YU ; Tonghai LIU ; Wen LI ; Senhao XIAO ; Lei FENG ; Jing HUANG ; Rong FU ; Jiacheng LI ; Liping LIU ; Mingchen WANG ; Hongru TAO ; Hualiang JIANG ; Kaixian CHEN ; Xingxing DIAO ; Bing ZHOU ; Xiaoyan SHEN ; Cheng LUO
Acta Pharmaceutica Sinica B 2022;12(11):4180-4192
Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.