1.Establishment and Application of an in Vitro Cellular Model of Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells with Serum Injury in aGVHD Mouse.
Run-Xiang XU ; Pei-Lin LI ; Jia-Yi TIAN ; Jie TANG ; Bo-Feng YIN ; Fu-Hao YU ; Fei-Yan WANG ; Xiao-Tong LI ; Xiao-Yu ZHANG ; Wen-Rong XIA ; Heng ZHU ; Li DING
Journal of Experimental Hematology 2025;33(1):255-261
OBJECTIVE:
To establish an in vitro cell model simulating acute graft-versus-host disease (aGVHD) bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells (MSCs).
METHODS:
The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model (n=20) was established by being injected with bone marrow cells (1×107 per mouse) from donor mice within 4-6 hours after receiving a lethal dose (8.0 Gy, 72.76 cGy/min) of γ ray general irradiation. A mouse model of aGVHD (n=20) was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells (1×107 per mouse) and spleen lymphocytes (2×106 per mouse). The blood was removed from the eyeballs and the mouse serum was aspirated on the 7th day after modeling. Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2%, 5% and 10% BMT mouse serum and aGVHD mouse serum in the medium, respectively. The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining. The expression levels of related proteins PPARγ and CEBPα were detected by Western blot. The expression differences of key adipogenic transcription factors including PPARγ, CEBPα, FABP4 and LPL were determined by real-time quantitative PCR (RT-qPCR).
RESULTS:
An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established. Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10% compared with BMT serum. Western blot experiments showed that adipogenesis-related proteins PPARγ and CEBPα expressed in MSCs were down-regulated. Further RT-qPCR assay showed that the production of PPARγ, CEBPα, FABP4 and LPL, the key transcription factors for adipogenic differentiation of MSC, were significantly reduced.
CONCLUSION
The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.
Animals
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Mesenchymal Stem Cells/cytology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Adipogenesis
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Female
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Cell Differentiation
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Graft vs Host Disease/blood*
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Bone Marrow Cells/cytology*
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PPAR gamma/metabolism*
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Disease Models, Animal
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CCAAT-Enhancer-Binding Protein-alpha/metabolism*
2.Dimeric natural product panepocyclinol A inhibits STAT3 via di-covalent modification.
Li LI ; Yuezhou WANG ; Yiqiu WANG ; Xiaoyang LI ; Qihong DENG ; Fei GAO ; Wenhua LIAN ; Yunzhan LI ; Fu GUI ; Yanling WEI ; Su-Jie ZHU ; Cai-Hong YUN ; Lei ZHANG ; Zhiyu HU ; Qingyan XU ; Xiaobing WU ; Lanfen CHEN ; Dawang ZHOU ; Jianming ZHANG ; Fei XIA ; Xianming DENG
Acta Pharmaceutica Sinica B 2025;15(1):409-423
Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.
3.Association of serum potassium trajectory with 30-day death risk in patients with sepsis in intensive care unit: a retrospective cohort study.
Shaoxu DENG ; Rui HUANG ; Fei XIA ; Tian ZHANG ; Longjiu ZHANG ; Jiangquan FU
Chinese Critical Care Medicine 2025;37(4):324-330
OBJECTIVE:
To investigate the relationship between the trajectories of serum potassium changes after intensive care unit (ICU) admission and 30-day death risk in patients with sepsis.
METHODS:
A retrospective cohort study was conducted, including adult patients with sepsis admitted to the comprehensive ICU, medical intensive care unit (MICU) and emergency intensive care unit (EICU) of Guizhou Medical University Affiliated Hospital from January 2020 to January 2024. The patients who had a minimum of 5 days' hospitalisation in the ICU and who had at least 7 consecutive days of the serum potassium measurements were classified into five trajectories groups according to group-based trajectory modelling (GBTM) using SAS software. This was based on tendency changes in serum potassium levels in patients after admission to the ICU, which was categorized as follows: slowly increased from a low level group, slowly increased from a medium level of normal range group, slowly decreased from a medium level of normal range group, slowly decreased from a high level group, and slowly increased from a high level of normal range group. The patient's gender, age, medical history, and white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), activated partial thromboplastin time (APTT), prothrombin time (PT), blood sodium, and serum creatinine (SCr) at the time of admission to the ICU were collected. At the same time, the patient's worst sequential organ failure assessment (SOFA) score within 24 hours of admission to the ICU, length of ICU stay, and 30-day outcome were record. The differences in clinical data among different groups of patients were compared. The 30-day cumulative survival rates of the various serum potassium trajectories were plotted using Kaplan-Meier survival curves, the groups were then compared using the Log-Rank test. A multivariate Cox proportional risk regression analysis was developed to evaluate the independent effect of serum potassium trajectory on 30-day death risk.
RESULTS:
Finally, 342 ICU sepsis patients were enrolled, of which 42 patients in the slowly increased from a low level group (12.28%), 127 patients in the slowly increased from a medium level of normal range group (37.14%), 118 patients in the slowly decreased from a medium level of normal range group (34.50%), 28 patients in the slowly decreased from a high level group (8.19%), and 27 patients in the slowly increased from a high level of normal range group (7.89%). Except for age and APTT differences, there were no statistically significant differences in other clinical characteristics among the patients in the different serum potassium trajectories groups. Kaplan-Meier survival curves showed that there was statistically significant difference in the 30-day cumulative survival rate among the patients in the different serum potassium trajectories groups (Log-Rank test: χ2 = 14.696, P = 0.005), with the lowest in the slowly increased from a high level of normal range group (39.3%). Multivariate Cox proportional risk regression analysis showed that the patients with the serum potassium trajectory of slowly increased from a high level of normal range had the highest 30-day death risk [hazard ratio (HR) = 2.341, 95% confidence interval (95%CI) was 1.049-5.226, P = 0.038]. This association persisted after adjustment for variables such as gender, age, medical history, SOFA score, WBC, PLT, PCT, APTT, PT, blood sodium, and SCr (HR = 3.058, 95%CI was 1.249-7.488, P = 0.014).
CONCLUSION
Compared with the patients whose serum potassium fluctuated within the normal range, the sepsis patients in the ICU with a serum potassium trajectory that slowly increased from a high level of normal range had a significantly higher 30-day death risk.
Humans
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Retrospective Studies
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Intensive Care Units
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Sepsis/blood*
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Potassium/blood*
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Male
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Female
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Middle Aged
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Aged
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Risk Factors
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Hospital Mortality
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Prognosis
4.Effect of IGFBP6 in unstable carotid atherosclerotic plaque:bioinformatics analysis and experimental validation
Yu-Yan LI ; Ying-Ying LIANG ; Jie-Xin ZHOU ; Fei CHE ; Jin-Xia FU
Medical Journal of Chinese People's Liberation Army 2024;49(6):701-710
Objective To investigate the differentially expressed genes(DEGs)and their molecular interactions in unstable carotid atherosclerotic plaques.Methods Gene expression datasets related to carotid atherosclerotic plaques(GSE41571,GSE118481,and E-MTAB-2055)were downloaded from Gene Expression Omnibus(GEO)and European Bioinformatics Institute(EBI)ArrayExpress databases.The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process(GO-BP),Kyoto Encyclopedia of Genes and Genomes(KEGG),Protein-Protein Interaction(PPI)Networks and subnetwork analysis,relationships between miRNAs/transcription factors and target genes,and drug-gene interaction database.Quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis.Results GO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes.KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor(ECM-receptor)interaction,PI3K-Akt,Hippo and transforming growth factor-β(TGF-β)signaling pathways,while downregulated DEGs were primarily enriched in lysosomes,phagosomes,and chemokines processes.PPI network analysis suggested that COL1A2,COL4A2,insulin-like growth factor binding protein 6(IGFBP6),COL4A5,C1QA,CXCL10,CXCL2,CXCR4,and CSF1R may play important roles in PPI networks.Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction,CXCL2 was most antagonized by drugs,and IGFBP6 was most activated by drugs.qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.001).ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.0001).Receiver operating characteristic(ROC)suggested that the area under the curve(AUC)for plasma IGFBP6 levels to identify unstable plaques was 0.894(95%CI 0.810-0.977),with a cutoff value of 142.08 ng/ml.Conclusion IGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.
5.Comparative study on cleansing effect of microbubble toothbrush and conventional pulsed oral irrigator
Ke-An YUE ; Wen-Xia HUANG ; Ming-Fu ZHANG ; Gui-Hua YAN ; Chang-Wei YANG ; Fei-Fei HONG ; Lu YIN
Chinese Medical Equipment Journal 2024;45(9):67-72
Objective To compare the oral cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator to provide references for users.Methods Ninety identical 3D-printed resin tooth models were grouped and subjected to repeated experiments,which were divided randomly into five groups including a microbubble toothbrush high-speed gear(GN-H)group,a microbubble toothbrush medium-speed gear(GN-M)group,a microbubble low-speed gear(GN-L)group,a conventional pulsed oral irrigator high-speed gear(W-H)group and a conventional pulsed oral irrigator low-speed gear(W-L)group,with 18 teeth in each group.The cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator were evaluated in terms of irrigating strength and abilities for eliminating plaque and debris.Results Both the two types of water flossers were provided with high irrigating strength and effectively reduced plaque and debris on tooth surfaces,and the GN-H,GN-M and GN-L groups behaved better significantly than the remained groups.The order of the five groups was GN-H group>GN-M group>W-H group>GN-L group>W-L group for irrigating strength,GN-H group>GN-M group>GN-L group>W-H group>W-L group for plaque removal,GN-H group>GN-M group>W-H group>GN-L group>W-L group for debris removal,with all the differences being statistically significant(P<0.05).Conclusion Both the two types of water flossers remove plaque and debris effectively,while the microbubble toothbrush gains advantages over the conventional pulsed oral irrigator.[Chinese Medical Equipment Journal,2024,45(9):67-72]
6.Research status of anti-inflammatory effect of traditional Chinese medicine based on NLRP3 inflammatory body
Fu-Mei XU ; Jun-Yuan ZENG ; Lei ZHAO ; Qi-Li ZHANG ; Peng-Fei XIA ; Yin-Qiang JIA ; Jie WANG ; Peng-Xia FANG ; Yan-Li XU
The Chinese Journal of Clinical Pharmacology 2024;40(6):923-927
Inflammasome is a kind of intracellular polyprotein complex,which is an important component of the complex system of local inflammatory microenvironment after human tissue damage.When the inflammasome is activated,it induces the activation of cysteine aspartate proteinase 1(caspase-1),mediates the maturation and secretion of proinflammatory cytokines,such as interleukin(IL)-1 β and IL-18,and induces cell death,which plays an important role in regulating the host immune response to pathogen infection and tissue repair of cell damage.Nod-like receptor protein 3(NLRP3)inflammatory body,which is composed of NLRP3,pro-cysteine aspartic acid specific protease-1(pro-caspase-1)and apoptosis-related spot-like protein(ASC),is the most deeply and widely studied type of inflammatory body,which plays an important role in the regulation of inflammation.When NLRP3 inflammatory bodies are activated,inflammatory mediators are produced and released,which participate in the occurrence and development of a variety of inflammatory diseases.Some studies have shown that traditional Chinese medicine can improve the pathological state of a variety of diseases by inhibiting NLRP3 inflammatory bodies,and play a role in the prevention and treatment of a variety of inflammatory diseases,including cardiovascular diseases,joint inflammation,diabetes and so on.This paper systematically combs the mechanism of NLRP3 inflammatory bodies,and summarizes the latest research reports on the effects of traditional Chinese medicine compound prescription,traditional Chinese medicine monomers and traditional Chinese medicine extracts on NLRP3 inflammatory bodies in the treatment of inflammatory diseases,in order to provide new ideas for the further study of the pathogenesis and drug treatment of many inflammatory diseases.
7.Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi
Jian Yu LIANG ; Hui Jia RONG ; Xiu Xue WANG ; Sheng Jian CAI ; Dong Li QIN ; Mei Qiu LIU ; Xu TANG ; Ting Xiao MO ; Fei Yan WEI ; Xia Yin LIN ; Xiang Shen HUANG ; Yu Ting LUO ; Yu Ruo GOU ; Jing Jie CAO ; Wu Chu HUANG ; Fu Yu LU ; Jian QIN ; Yong Zhi ZHANG
Biomedical and Environmental Sciences 2024;37(1):3-18
Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.
8.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.
9.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
10.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

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