1.Effect of the multidisciplinary management model on the prognosis of patients with portal hypertension
Changxiang LAI ; Qiyuan TANG ; Zhiyu LI ; Yujin JIANG ; Xuan ZHOU ; Wenjie XIAN ; Ruikun CHEN ; Xiaojuan WU ; Qing HE ; Fang WANG
Journal of Clinical Hepatology 2025;41(10):2068-2074
ObjectiveTo investigate the effect of the multidisciplinary team (MDT) management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled, and according to whether the MDT treatment regimen was implemented, they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected, and the patients were observed in terms of gastrointestinal bleeding, hepatic encephalopathy, liver cancer, and death from admission to the end of follow-up (January 2025). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events (gastrointestinal bleeding, hepatic encephalopathy, liver cancer, and death), and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein (t=1.216, P=0.017) and ascites (χ2=4.515, P=0.034) at baseline. The patients were followed up for 14.6±6.2 months, and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups (χ2=4.573, P=0.024), while there were no significant differences in the incidence rates of other outcome events between the two groups (all P>0.05). The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding (hazard ratio=0.262, 95% confidence interval: 0.110 — 0.630, P=0.003). ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension, while its long-term benefits require further follow-up verification.
2.Active monitoring and analysis of hypoglycemia in hospitalized diabetic patients
Lu LIN ; Luchuan ZHAN ; Shuting ZHANG ; Yongjie LI ; Xiaojuan ZHANG ; Laiyou WANG ; Weihua LAI
Chongqing Medicine 2025;54(8):1870-1876,1882
Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.
3.Expert consensus: reducing free-sugar for caries prevention
Xiaojuan ZENG ; Xuenan LIU ; Min LIU ; Yan SI ; Ying ZHANG ; Jianqiang LAI ; Xianbin DING ; Chang SU ; Xiang SI ; Youguang LU ; Huancai LIN ; Shuguo ZHENG ; Wensheng RONG ; Minquan DU ; Xiaoyan OU ; Rongmin QIU ; Maigeng ZHOU ; Chunxiao WANG
Chinese Journal of Stomatology 2025;60(4):311-319
In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.
4.Expert consensus: reducing free-sugar for caries prevention
Xiaojuan ZENG ; Xuenan LIU ; Min LIU ; Yan SI ; Ying ZHANG ; Jianqiang LAI ; Xianbin DING ; Chang SU ; Xiang SI ; Youguang LU ; Huancai LIN ; Shuguo ZHENG ; Wensheng RONG ; Minquan DU ; Xiaoyan OU ; Rongmin QIU ; Maigeng ZHOU ; Chunxiao WANG
Chinese Journal of Stomatology 2025;60(4):311-319
In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.
5.Establishment of a noninvasive predictive model for antiviral therapy in patients with chronic hepatitis B virus infection and an age of≤30 years
Changxiang LAI ; Qingrong TANG ; Xiulian ZHANG ; Qiyuan TANG ; Zhiyu LI ; Xuan ZHOU ; Wenjie XIAN ; Ruikun CHEN ; Xiaojuan WU ; Fang WANG
Journal of Clinical Hepatology 2024;40(7):1328-1333
Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95%confidence interval[CI]:0.2—1.0),STE(OR=1.5,95%CI:1.0—2.1),and PIIIP(OR=1.1,95%CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34%and a sensitivity of 96.36%,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.
6.Changes of physical fitness before and after regular aerobic exercise in children after radical pulmonary atresia surgery
Xiaowei LI ; Xiaotong LAI ; Yunting LI ; Chenghao ZHANG ; Jiaxin ZHUANG ; Junhao CHEN ; Shufang LIU ; Wenjing LI ; Xiaojuan ZHENG ; Yugong GUO ; Yanqin CUI
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):672-679
Objective:To examine the effect of short-term regular aerobic exercise on physical fitness of children with pulmonary with atresia ventricular septal defect after radical biventricular treatment.Methods:This was a prospective self pre-and post-control observation study. The subjects performed regular aerobic exercise for 10 days according to the exercise prescription. Body composition measurement and cardiopulmonary exercise test[lung ventilation function, maximum oxygen uptake(VO 2max), maximum oxygen pulse(O 2/HR max), ventilation oxygen uptake efficiency(OUES), exercise load time], 6 min walking distance(6MWD), sports psychometric test, motor function screening test and fitness test, were collected. The changes of test parameters and scale scoring before and after exercise were analyzed and compared. Results:A total of 7 children with PA/VSD after biventricular surgery were enrolled. The age ranged 8.2-16.2 years old, and there were 2 males and 5 females. VO 2max[(1 196.71±395.31)ml/min vs.(1 297.43±425.73)ml/min, P=0.031], O 2/HRmax[(82.43±7.53)ml/beat vs.(91.57±6.95)ml/beat, P<0.001]increased after exercise. The exercise load time was significantly increased compared with that before intervention[(476.43±35.73)s vs.(531.43±45.76)s, P=0.002]. Resting heart rate before exercise( P=0.013) and peak respiration exchange ratio(PeakRER, P=0.021) were significantly lower. Body composition tests suggest weight, intracellular water, protein and muscle content of lower limb were higher( P<0.05). The motor function score was higher than before( P=0.015); the score of sports fear was lower than before( P=0.009). There was no significant difference in lung capacity and 6-minute walking distance before and after exercise( P>0.05). There were no cardiovascular events during the study period. Conclusion:Short-term regular aerobic exercise for children with PA/VSD after biventricular surgery can improve exercise tolerance, increase lower limb muscle content, improve exercise fear and exercise function, and has good safety and feasibility.
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Impact of blood pressure variability on occurrence of acute kidney injury in patients with hypovolemic shock
Meng YANG ; Qiuxiang HU ; Xiaojuan LAI ; Yanmei HUANG
Modern Clinical Nursing 2024;23(12):1-8
Objective To explore the relationship between the variability of blood pressure and the occurrence of acute kidney injury(AKI)in patients with hypovolemic shock so as to provide a theoretical basis for early prediction and prevention of AKI.Methods Clinical data of 661 critically ill patients with hypovolemic shock were acquired from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database from 2008 to 2022.Data were grouped with the quartile division method,with systolic blood pressure average real variability(SBP-ARV)and diastolic blood pressure average real variability(DBP-ARV)as the continuous or categorical variables.Univariate and multivariate logistic regression analyses were used to examine the relationships of SBP-ARV and DBP-ARV with the occurrence of AKI.Additionally,the relationship between SBP-ARV and the occurrence of AKI was further investigated in subgroups of gender,age,sequential organ failure assessment(SOFA),hypertension,diabetes,and the use of vasopressors after correction of all covariates.Results Logistic regression analysis showed that SBP-ARV,a continuous variable,was independently associated with the occurrence of AKI[OR(95%CI):1.05(1.01~1.10),P=0.024].However,DBP-ARV was not significantly related to the occurrence of AKI.When SBP-ARV was grouped by quartile division,Q4 group had a significantly higher risk of AKI[OR(95%CI):1.83(1.04~3.22),P=0.037]compared with that of Q1 group.Analyses across the subgroups revealed that there was an interaction between SBP-ARV and diabetes(P=0.033).Conclusion For ICU patients with hypovolemic shock,SBP-ARV positively associates with the occurrence of AKI.
9.Impact of blood pressure variability on occurrence of acute kidney injury in patients with hypovolemic shock
Meng YANG ; Qiuxiang HU ; Xiaojuan LAI ; Yanmei HUANG
Modern Clinical Nursing 2024;23(12):1-8
Objective To explore the relationship between the variability of blood pressure and the occurrence of acute kidney injury(AKI)in patients with hypovolemic shock so as to provide a theoretical basis for early prediction and prevention of AKI.Methods Clinical data of 661 critically ill patients with hypovolemic shock were acquired from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database from 2008 to 2022.Data were grouped with the quartile division method,with systolic blood pressure average real variability(SBP-ARV)and diastolic blood pressure average real variability(DBP-ARV)as the continuous or categorical variables.Univariate and multivariate logistic regression analyses were used to examine the relationships of SBP-ARV and DBP-ARV with the occurrence of AKI.Additionally,the relationship between SBP-ARV and the occurrence of AKI was further investigated in subgroups of gender,age,sequential organ failure assessment(SOFA),hypertension,diabetes,and the use of vasopressors after correction of all covariates.Results Logistic regression analysis showed that SBP-ARV,a continuous variable,was independently associated with the occurrence of AKI[OR(95%CI):1.05(1.01~1.10),P=0.024].However,DBP-ARV was not significantly related to the occurrence of AKI.When SBP-ARV was grouped by quartile division,Q4 group had a significantly higher risk of AKI[OR(95%CI):1.83(1.04~3.22),P=0.037]compared with that of Q1 group.Analyses across the subgroups revealed that there was an interaction between SBP-ARV and diabetes(P=0.033).Conclusion For ICU patients with hypovolemic shock,SBP-ARV positively associates with the occurrence of AKI.
10.IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.
Juan LIU ; Yuxin ZHUANG ; Jianlin WU ; Qiang WU ; Meixian LIU ; Yue ZHAO ; Zhongqiu LIU ; Caiyan WANG ; Linlin LU ; Yingjiao MENG ; Kawai LEI ; Xiaojuan LI ; Qibiao WU ; Elaine Lai-Han LEUNG ; Zhengyang GUO ; Liang LIU ; Ting LI
Acta Pharmaceutica Sinica B 2022;12(2):651-664
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

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