1.Value of indocyanine green clearance test combined with total bilirubin actual resident rate in evaluating the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure after artificial liver support system therapy
Honglian DU ; Ye LI ; Bo WANG ; Linkun MA ; Tiantian HU ; Yunjian SHENG ; Wen CHEN ; Gang WU ; Cunliang DENG
Journal of Clinical Hepatology 2023;39(2):307-315
Objective To establish a new model of indocyanine green (ICG) clearance test combined with total bilirubin actual resident rate (TBARR) for predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with artificial liver support system (ALSS) therapy. Methods A retrospective analysis was performed for the clinical data of 136 patients with HBV-ACLF who underwent ALSS therapy in Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, from June 2017 to July 2021, and according to the prognosis at 3-month follow-up, they were divided into survival group with 92 patients and death group with 44 patients. Related indicators were measured at the time of the confirmed diagnosis of ACLF, including biochemical parameters, coagulation, indocyanine green retention rate at 15 minutes (ICGR 15 ), and effective hepatic blood flow (EHBF), and related indices were calculated, including Model for End-Stage Liver Disease (MELD) score, MELD difference (ΔMELD), Child-Turcotte-Pugh (CTP) score, total bilirubin clearance rate (TBCR), total bilirubin rebound rate (TBRR), and TBARR. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used to establish a combined predictive model for the prognosis of HBV-ACLF after ALSS therapy. The area under the ROC curve (AUC) was used to compare the accuracy of various models in judging the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the Z test was used for comparison of AUC. Results There were significant differences between the death group and the survival group in MELD score, ΔMELD, CTP score, ICGR 15 , EHBF, TBRR, TBARR, neutrophil count, percentage of neutrophils, lymphocyte count, platelet count, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, albumin, prothrombin time, international normalized ratio, prothrombin time activity, prealbumin, fibrinogen, serum sodium, age, and the incidence rate of hepatic encephalopathy (all P < 0.05). The multivariate logistic regression analysis showed that age (odds ratio [ OR ]=1.096, 95% confidence interval [ CI ]: 1.056-1.137, P < 0.001), neutrophil count ( OR =1.214, 95% CI : 1.044-1.411, P =0.012), TBRR ( OR =0.989, 95% CI : 0.982-0.996, P =0.001), TBARR ( OR =1.073, 95% CI : 1.049-1.098, P < 0.001), ΔMELD ( OR =1.480, 95% CI : 1.288-1.701, P < 0.001), CTP score ( OR =2.081, 95% CI : 1.585-2.732, P < 0.001), and ICGR 15 ( OR =1.116, 95% CI : 1.067-1.168, P < 0.001) were independent influencing factors for short-term mortality in patients with HBV-ACLF after ALSS therapy. The binary logistic regression analysis was used to establish four combined predictive models for predicting the prognosis of HBV-ACLF after ALSS therapy, i.e., TBRR-ICGR 15 , TBARR-ICGR 15 , TBARR-ICGR 15 -ΔMELD, and TBARR-ICGR 15 -ΔMELD-age, with an AUC of 0.830, 0.867, 0.900, and 0.917, respectively, and the combined predictive models had a larger AUC than each index alone (age, neutrophil count, TBRR, TBARR, ΔMELD, MELD score, CTP score, and ICGR 15 ), among which the TBARR-ICGR 15 -ΔMELD-age model had the largest AUC. The combined models TBARR-ICGR 15 -ΔMELD and TBARR-ICGR 15 -ΔMELD-age had sensitivities and specificities of > 80%. Conclusion The combined predictive model established by ICGR 15 and TBARR has a good value for in predicting the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the combined predictive model has a better accuracy than the single model in judging prognosis.
2.Value of albumin-related ratios in predicting the risk of death in patients with hepatitis B virus-related acute-on-chronic liver failure
Yu ZENG ; Hang WANG ; Cunliang DENG ; Yunjiang SHENG
Journal of Clinical Hepatology 2023;39(11):2580-2587
ObjectiveTo investigate and compare the value of albumin-related ratios [total bilirubin-to-albumin ratio (TAR), creatinine-to-albumin ratio (CAR), prothrombin time-international normalized ratio-to-albumin ratio (IAR), neutrophil count-to-albumin ratio (NAR), and red blood cell distribution width-to-albumin ratio (RAR)] in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). MethodsA retrospective analysis was performed for 354 patients with HBV-ACLF who were admitted to Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, from June 2017 to February 2022, and according to their prognosis at 3 months of follow-up, they were divided into survival group (n=272) and death group (n=82). Related indices were recorded for all patients, including age, sex, complications, and the results of routine blood test, liver function, and coagulation for the first time after admission, and albumin-related ratios and Model for End-Stage Liver Disease (MELD) score were calculated. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distribution continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman correlation test was used to investigate the correlation between albumin-related ratios and MELD score. The Logistic regression analysis was used to explore the association of MELD score, TAR, CAR, IAR, NAR, and RAR with poor prognosis. The area under the ROC curve (AUC) was used to as sess the accuracy of albumin-related ratios and MELD score in predicting the short-term prognosis of HBV-ACLF patients, and the De-Long test was used for the comparison of AUC. ResultsCompared with the death group, the survival group had significantly lower MELD score (Z=-8.071, P<0.001), TAR (Z=-6.695, P<0.001), CAR (Z=-4.463, P<0.001), IAR (Z=-7.912, P<0.001), NAR (Z=-4.061, P<0.001), and RAR (Z=-4.788, P<0.001). MELD score was positively correlated with CAR (r=0.616, P<0.001), IAR (r=0.733, P<0.001), TAR (r=0.657, P<0.001), NAR (r=0.392, P<0.001), and RAR (r=0.380, P<0.001). The multivariate regression analysis of MELD score and albumin-related ratios showed that high TAR (odds ratio [OR]=1.014, 95% confidence interval [CI]: 1.008 — 1.020, P<0.001) and high IAR (OR=22.052, 95%CI: 6.937 — 70.103, P<0.001) were independent risk factors for death. The ROC curves were plotted for albumin-related ratios and MELD score to evaluate their discriminatory ability for mortality, and the results showed that MELD score, TAR, CAR, IAR, NAR, and RAR had an AUC of 0.794, 0.744, 0.663, 0.788, 0.648, and 0.674, respectively, among which MELD score had the highest sensitivity of 86.59% and CAR had the highest specificity of 77.57%. TAR combined with IAR had an AUC of 0.809, with a sensitivity of 76.8% and a specificity of 71.3%. Subgroup analysis of HBV-ACLF showed that TAR combined with IAR had the highest AUC values of 0.884 and 0.733, respectively, in patients with type A or type C HBV-ACLF. ConclusionTAR and IAR can be used as simple and effective prognostic tools to predict the 90-day mortality of HBV-ACLF patients.
3.MicroRNA 424-5p promotes the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting Kinesin family member 23
Xiaoling LIU ; Changfeng SUN ; Yue YUAN ; Yunjian SHENG ; Cunliang DENG
Chinese Journal of Hepatology 2022;30(10):1074-1081
Objective:To explore the effect of MicroRNA 424-5p/Kinesin family member 23(miR-424-5p/KIF23)axis on the malignant phenotype of hepatoma cells and its sensitivity of sorafenib.Methods:Real-time quantitative reverse PCR(qRT-PCR) and/or Western blot were used to detect the expression of miR-424-5p and KIF23 in liver cancer tissues and paracancerous tissues, human hepatocellular carcinoma(HCC) cells HepG2 and normal hepatocyte LO2. HepG2 cells transfected with miR-424-5p mimic and miR-424-5p mimic NC were respectively defined as miR-424-5p mimic group and mimic NC group, HepG2 cells transfected with KIF23 overexpression vector pcDNA3.1-KIF23 or empty vector pcDNA3.1 respectively were defined as OE-KIF23 group and Vector group, and HepG2 cells co-transfected with miR-424-5p mimic and overexpression vector pcDNA3.1-KIF23 were defined as mimic+OE-KIF23 group: The KIF23-3'UTR wild-type vector (KIF23-WT) and the mutant vector (KIF23-MT) were co-transfected with miR-424-5p micic and mimic NC, respectively, and the targeting relationship between miR-424-5p and KIF23 was verified by dual-luciferase reporting experiments. The cell counting Kit-8 (CCK-8) was used to detect HepG2 cell proliferation and sensitivity to sorafenib. Flow cytometry was used to assess apoptosis in HepG2 cells. Transwell and scratch experiments were used to detect HepG2 cell migration and invasion capabilities. Intergroup data were compared using t-tests or analysis of variance. Results:Compared with the paracancerous tissue and normal hepatocytes, miR-424-5p in the HCC tissue and hepatocellular cells was significantly down-regulated (the relative expression was 0.604±0.121, 0.585±0.064), and KIF23 was significantly up-regulated (the relative expression was 5.451±1.834, 2.482±0.545), P<0.05. miR-424-5p mimic can inhibit the proliferation, migration and invasion of HCC cells and promote apoptosis of HCC cells ( P<0.05). Overexpression of KIF23 can promote the proliferation, migration and invasion of HCC cells and inhibit apoptosis of HCC cells ( P<0.05). The luciferase activity of HepG2 cells in the mimic and KIF23-WT co-transfection groups was significantly reduced compared with HepG2 cells in the mimic NC and KIF23-WT co-transfection groups (the relative fluorescence intensities were 3.668±0.091 and 2.629±0.056, respectively, P<0.05),however, there was no significant comparison between the luciferase activity of cells in the mimic and KIF23-MT co-transfection groups compared with those in the mimic NC and KIF23-MT co-transfection groups. miR-424-5p mimic can reverse the role of overexpression of KIF23 in promoting the ability of HCC cells to proliferate, migrate and invade ( P<0.05). The inhibition rates of sorafenib on HepG2 cells in the mimic+OE-KIF23 group and the OE-KIF23 group were 47.491%±3.863% and 36.246%±6.063% ( t=3.027, P<0.05). Conclusion:miR-424-5p can inhibit the proliferation, migration and invasion of HCC cells and can increase the sensitivity of HCC cells to sorafenib by targeting the expression level of KIF23.
4.Efficacy of plasma exchange combined with dual plasma molecular adsorption system in the treatment of patients with hepatitis B virus related acute-on-chronic liver failure
Qing YANG ; Qiang GENG ; Changfeng SUN ; Xiaoling LIU ; Shiyu SUN ; Yunjian SHENG ; Cunliang DENG
Chinese Journal of Infectious Diseases 2021;39(7):430-435
Objective:To investigate the clinical efficacy of plasma exchange combined with dual plasma molecular adsorption system (PE+ DPMAS) in treating patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 114 HBV-ACLF patients admitted to The Affiliated Hospital of Southwest Medical University in Luzhou City and treated with PE+ DPMAS from June 2014 to January 2018 were included. According to different basis of liver diseases, there were type A, type B and type C. The laboratory data and model for end-stage liver disease (MELD) of patients before PE+ DPMAS and 48 h after treatment, and the prognosis of patients at 90 d were retrospectively analyzed. Independent sample t test, paired sample t test, nonparametric test, variance analysis and chi-square test were used for statistical analysis. Results:The clinical stages among patients with type A (22 cases), type B (39 cases) and type C (53 cases) were mainly early (seven, 17, 22 cases) and mid-stages (eight, 14, 20 cases). Before PE+ DPMAS, alanine aminotransferase (ALT), prealbumin (pAlb), albumin (Alb), creatinine (Cr), total bilirubin (TBil), prothrombin time (PT), international normalized ratio (INR), prothrombin activity (PTA), and MELD were all not statistically different among the patients in the three groups (all P>0.05). After PE+ DPMAS treatment, ALT, TBil, PT, INR, MELD, pAlb, Alb, and PTA in patients with type A were statistically different compared with those before treatment ( Z=5.104, t=5.555, 4.974, 4.481, 7.984, -5.396, -2.784 and -6.752, respectively, all P<0.05). ALT, TBil, PT, INR and MELD in patients with type B were significantly decreased, while pAlb and PTA were significantly increased after treatment ( Z=-5.428, t=4.867, 4.405, 4.179, 6.186, -6.290 and -4.533, respectively, all P<0.01). ALT, pAlb and TBil in patients with type C after PE+ DPMAS treatment were significantly different from those before treatment ( Z=-5.723, t=-2.525 and 2.462, respectively, all P<0.05). There was no statistically significant difference in Cr of the three groups before and after treatment (all P>0.05). The patients with type A had the shortest hospital stay ((17.95±5.92) d), while the patients with type C had the longest stay ((25.77±7.02) d). The hospital stay of patients with type B was (21.79±6.72) d. The difference was statistically significant ( F=11.317, P<0.01). After 90 d follow-up, four patients (18.18%) with type A died, nine patients (23.08%) with type B died, and 25 patients (47.17%)with type C died. The difference was statistically significant ( χ2=8.615, P=0.013). Conclusion:HBV-ACLF patients with type A and type B have better prognosis after PE+ DPMAS treatment compared to patients with type C who are in the decompensated stage of liver cirrhosis.
5.Effective Evaluation of Medical Cooperation with D.Menu Style
Jing WEN ; Zhengjun CHEN ; Cunliang DENG ; Chengyu YIN ; Zhangquan LUO ; Xiaolong WANG
Modern Hospital 2017;17(5):629-631
Objective To understand the effectiveness of medical cooperation in the Affiliated Hospital of Southwest Medical University with a county hospital for providing a reference basis for medical cooperation.
6.Effects of high glucose and insulin on the mRNA expressions of TGF-β1 , and TIMP-1 of hepatic stellate cells in rat
Journal of Chinese Physician 2016;18(8):1194-1197
Objective To explore the mechanism of diabetic hepatic fibrosis by observing effects of high glucose and insulin on expressions of transforming growth factor beta 1 (TGF-β1) and tissue inhibitor of metalloproteinase (TIMP-1) mRNAs of hepatic stellate cell (HSC) in rat.Methods Hepatic stellate cell lines in vitro were administrated by different dose of glucose without insulin and glucose with insulin for 72 h,and mannitol was chosen as hyperosmosis control group.Real time fluorescent quantitation polymerase chain reaction (RT-FQ-PCR) was used to determine expressions of TGF-β1 and TIMP-1 mRNAs of HSC in each group.Results Expressions of TGF-β1 and TIMP-1 mRNAs of HSC in each group could be detected and showed no significant difference among groups (P > 0.05).However,in general,expression of TGF-β1 mRNA in glucose with insulin group decreased and TIMP-1 mRNA increased.Conclusions The mRNA expressions of TGF-β1 and TIMP-1 in HSC could not be induced by high glucose alone,high dose of insulin may increase expressions of HSC TIMP-1 and reduce TGF-β1 expression.The main mechanisms of diabetic hepatic fibrosis may not be TGF-β1 pathway but be closely related to TIMP-1 pathway.
7.The expression and clinical significance of augmenter of liver regeneration in patients with HBV related acute on chronic liver failure
Chun YANG ; Wen CHEN ; Cunliang DENG ; Yiliang BI ; Li TANG ; Gang WU
Chongqing Medicine 2014;(20):2579-2581
Objective To investigate the expression and clinical significance of augmenter of liver regeneration (ALR) in patients with HBV related acute on chronic liver failure (ACLF) .Methods The serum and clinical data of patients with ACLF (ACLF group ,n=214) ,patients with mild chronic hepatitis B (mild chronic hepatitis B group ,n=196) were collected from outpatient and inpatient in the hospital ,and control group(n=200) people were the blood transfusion healthy blood donors .The level of ALR was measured by ELISA method .The correlation between ALR and MELD score of patients with ACLF were analyzed by linear regres-sion analysis .Unconditioned binary response logistic regression model was used to determine the correlation between ALR and mor-tality at 24 weeks of patients with ACLF .Results Serum ALR level was higher in ACLF group than in mild chronic hepatitis B group and control group(P<0 .05) .There were negative correlations between the serum ALR level and MELD score of patients with ACLF(r2 = -0 .249 ,F=13 .955 ,P<0 .01) .Serum ALR level of patients with ACLF was more significant in survival group than in dead group(P=0 .004) .Logistic regression analysis identified that high serum ALR level was related to the good prognosis (P=0 .012 ,OR=0 .807) .Conclusion The serum ALR level was significantly increased in patients with HBV related ACLF which played an important role in liver regeneration and improve the prognosis of patients .
8.Efficacy observation of sequential plasma perfusion of low dose plasma exchange in patients with acute on chronic liver failure
Gang WU ; Wen CHEN ; Cunliang DENG ; Li TANG ; Bo QIN
Chongqing Medicine 2014;(25):3281-3283
Objective To investigate the clinical efficacy of sequential plasma perfusion of low dose plasma exchange in the pa-tients with acute on chronic liver failure (ACLF).Methods The patients with HBV related ACLF in the infection department of the Affiliated Hospital of Luzhou Medical College were divided into the plasma exchange therapy group (group A,n=114)and the low dose plasma exchange sequential plasma perfusion therapy group (group B,n=144).The group A was treated only by plasma exchange of fresh frozen plasma 2 400 mL;while the group B adopted the sequential plasma perfusion of plasma exchange,with fresh frozen plasma dosage of 1 400 mL.The changes of the liver and renal function,coagulation function and electrolyte indicators were observed in the two groups.The differences in the clinical effects and adverse reactions were compared between the two groups.Results The serum levels of ALT,TBIL and INR after treatment in the two groups were significant decreased than before treatment(P<0.05);ALB and PTA were significantly improved compared with before treatment(P<0.05);there were no signif-icant differences in serum levels of CRE,K+ and Na+ between before and after treatment.The changes of various indexes before and after treatment had no statistical differences between the two groups.The total effective rate and the mortality at 24 weeks in the group B was 66.66% and 47.22% respectively,which had no statistical differences compared with the group A.The total oc-currence rate of adverse reactions in the group B was 23.75%,which was significant lower than 35.26% in the group A with statis-tical difference (P=0.011).Conclusion Sequential plasma perfusion of plasma exchange has better clinical effect and few adverse reactions for treating the patients with ACLF,which can reduce the plasma dosage significantly.
9.Clinical features of patients with superinfection of HEV and HBV related acute on chronic liver failure
Wen CHEN ; Chun YANG ; Cunliang DENG ; Ni TANG ; Gang WU
Chongqing Medicine 2014;(30):4007-4009
Objective To investigate the clinical features of patients with superinfection of HEV and HBV related acute on chro-nic liver failure(ACLF) .Methods Clinical data of 35 patients diagnosed with superinfection of HEV and HBV related ACLF and 37 patients diagnosed with HBV related ACLF were collected for this retrospective study .The liver and kidney function ,HBV DNA level ,blood platelet count(BPC) ,coagulation function ,model for end-stage liver disease(MELD)score and mortality at 24 weeks were analyzed .Furthermore ,comparison of the clinical data between the survival patients and died patients in superinfection group was made .Unconditioned binary response logistic regression model was used to determine the corresponding risk factors .Results The level of total bilirubin(TBIL) ,MELD score ,incidence rate of hepatic encephalopathy and mortality at 24 weeks were signifi-cantly higher and prothrombin activity(PTA)was significantly lower in superinfection patients(P<0 .05) .The level of serum creat-inine(Cr) ,MELD score and incidence rate of hepatic encephalopathy were significantly higher and PTA was significantly lower in died patients than that of superinfection group(P< 0 .05) .Logistic regression analysis identified TBIL(P= 0 .024 ,OR= 1 .006) , BPC(P=0 .019 ,OR=0 .983) ,PTA(P=0 .001 ,OR=0 .795) ,MELD score(P=0 .005 ,OR=1 .497)and hepatic encephalopathy(P=0 .001 ,OR=4 .147)as prognostic factors for patients with superinfection of HEV and HBV related ACLF .Conclusion The clini-cal features of patients with superinfection of HEV and HBV related ACLF were more serious .The higher level of TBIL ,MELD score and hepatic encephalopathy and the lower level of BPC and PTA ,the worse prognosis .
10.Role and mechanism of Astragalus in alleviating adhesion of neutrophils to human renal tubular cells induced by postasphyxial-serum of neonate
Hongyu YANG ; Wenbin DONG ; Qingping LI ; Xiaoping LEI ; Tao XIONG ; Cunliang DENG ; Feng CHEN
Journal of Clinical Pediatrics 2009;(11):1070-1073
Objective To investigate the role of Astragahs in alleviating adhesion of neutrophils to HK-2 cells induced by postasphyxial-serum of neonate and its signal transduction mechanism. MethodsHK-2 cells were used as target cell. Control group, asphyxia group, Astragalus group were divided in the experiment. The 20% (volume fraction) postasphyxial-serum was used as attacking factor. The following indicators were detected: cellular morphology and neutrophils adhesion were observed with inverted microscope. The activity of myeloperoxidase (MPO) in the cell suspension were determined by biochemistry assay as the indicator for adhesion of neutrophils to HK-2. Intercellular adhesion molecule-1(ICAM-1) were examined by flow eytometer. ResultsThe neutrophils numbers (MPO activity) and ICAM-1 expression in asphyxia group were higher than that of the control group, but dramatically decreased in Astragalus group (P < 0.05). ConclusionsThese data demonstrated that Astragalus could alleviate the adhesion of neutrophils from neonate with asphyxia to HK-2 and it' s intracellular signal transduction mechanism is presumably involved in the inhibition of ICAM-1 expression on HK-2 cellular membrane.

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