1.Coagulation abnormalities in acute decompensated cirrhosis comorbid with infection: A prospective observational study based on thromboelastography
Ruiqing ZHANG ; Shumin CAI ; Xiuhua JIANG ; Jianming HUANG ; Beiling LI ; Jinjun CHEN
Journal of Clinical Hepatology 2025;41(5):907-913
ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis (ADC) patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023, among whom there were 86 patients with sepsis and 30 patients without sepsis, and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography (TEG) and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected, and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis, the lungs and bloodstream were the main infection sites, and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone, the patients with ADC and sepsis had a significant reduction in median maximum amplitude (MA), a significant increase in coagulation time (K time), and a significant reduction in α angle (all P<0.05); the patients with ADC and sepsis had a significantly longer reaction time (R time) than those with ADC alone (P=0.02), and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis (P=0.04). There was no correlation between MA and platelet count in the patients with ADC and sepsis (r=-0.133, P=0.057), while there was a significant correlation between MA and platelet count in the patients with sepsis alone (r=0.595, P=0.001). SOFA score was negatively correlated with MA in sepsis patients with or without ADC (r=-0.503 and -0.561, both P<0.001), and for the patients with ADC and sepsis, R time, K time, and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT (all P<0.05). The patients with ADC alone all survived within 90 days, and compared with the death group, the patients with sepsis alone who survived had significantly higher values of MA and α angle (all P<0.05); there was a significant difference in α angle on day 90 between the survival group and the death group, no matter whether the patients were comorbid with ADC or not (both P<0.01), while for the patients with ADC and sepsis, there was no significant difference in MA value on day 90 between the survival group and the death group (P>0.05). ConclusionFor ADC patients comorbid with sepsis, coagulation function assessment and monitoring should be taken seriously in clinical practice, and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.
2.Trace component fishing strategy based on offline two-dimensional liquid chromatography combined with PRDX3-surface plasmon resonance for Uncaria alkaloids.
Hui NI ; Zijia ZHANG ; Ye LU ; Yaowen LIU ; Yang ZHOU ; Wenyong WU ; Xinqin KONG ; Liling SHEN ; Sihan CHEN ; Huali LONG ; Cheng LUO ; Hao ZHANG ; Jinjun HOU ; Wanying WU
Journal of Pharmaceutical Analysis 2025;15(9):101244-101244
The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C18 column and a conventional C18 column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H2O2 measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H2O2 clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.
3.Coagulation abnormalities in acute decompensated cirrhosis comorbid with infection:A prospective observational study based on thromboelastography
Ruiqing ZHANG ; Shumin CAI ; Xiuhua JIANG ; Jianming HUANG ; Beiling LI ; Jinjun CHEN
Journal of Clinical Hepatology 2025;42(5):907-913
Objective To investigate the changes in coagulation system in acute decompensated cirrhosis(ADC)patients with or without sepsis and the association of these changes with short-term prognosis.Methods A prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023,among whom there were 86 patients with sepsis and 30 patients without sepsis,and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group.Thromboelastography(TEG)and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients.The data including TEG results and short-term prognosis were collected,and a correlation analysis was performed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman correlation coefficient was calculated to investigate the correlation between different variables.The Logistic regression model was used to perform the univariate and multivariate analyses.Results For the ADC patients with sepsis,the lungs and bloodstream were the main infection sites,and bacteria were the main pathogenic microorganism.TEG results showed that compared with the patients with sepsis alone,the patients with ADC and sepsis had a significant reduction in median maximum amplitude(MA),a significant increase in coagulation time(K time),and a significant reduction in α angle(all P<0.05);the patients with ADC and sepsis had a significantly longer reaction time(R time)than those with ADC alone(P=0.02),and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis(P=0.04).There was no correlation between MA and platelet count in the patients with ADC and sepsis(r=-0.133,P=0.057),while there was a significant correlation between MA and platelet count in the patients with sepsis alone(r=0.595,P=0.001).SOFA score was negatively correlated with MA in sepsis patients with or without ADC(r=-0.503 and-0.561,both P<0.001),and for the patients with ADC and sepsis,R time,K time,and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT(all P<0.05).The patients with ADC alone all survived within 90 days,and compared with the death group,the patients with sepsis alone who survived had significantly higher values of MA and α angle(all P<0.05);there was a significant difference in α angle on day 90 between the survival group and the death group,no matter whether the patients were comorbid with ADC or not(both P<0.01),while for the patients with ADC and sepsis,there was no significant difference in MA value on day 90 between the survival group and the death group(P>0.05).Conclusion For ADC patients comorbid with sepsis,coagulation function assessment and monitoring should be taken seriously in clinical practice,and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.
4.Characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction
Yichen YAO ; Haiyu WANG ; Lin DAI ; Qian WANG ; Ranran XI ; Junting WAN ; Jinjun CHEN
Journal of Clinical Hepatology 2025;41(8):1571-1578
Objective To retrospectively study the characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction,and to inform the clinical diagnosis and treatment of decompensated liver cirrhosis.Methods We retrospectively analyzed the clinical data of patients with liver cirrhosis and diastolic heart dysfunction admitted to Nanfang Hospital of Southern Medical University from April 1,2019 to July 31,2023.The patients were divided into compensated cirrhosis group(n=37)and decompensated cirrhosis group(n=226),and those with decompensated cirrhosis were further divided into subgroups of patients with heart dysfunction(n=84)and patients without heart dysfunction(n=142).We compared two groups using the independent samples t-test and Mann-Whitney U test for continuous data in normal distribution and data in skewed distribution,respectively;compared multiple groups using the Kruskal-Wallis H test,with subsequent paired comparisons using the Wilcoxon test;compared categorical data between two groups using the chi-square test or corrected chi-square test;identified the factors affecting patient survival using a Logistic regression model;and plotted Kaplan-Meier survival curves,with inter-group comparisons using the log-rank test.Results A total of 263 eligible patients were ultimately included,among whom 226 patients were diagnosed with decompensated liver cirrhosis(84 patients with diastolic dysfunction).Between the diastolic dysfunction group and non-diastolic dysfunction group,significant differences were detected in age(t=-4.566,P<0.05),activated partial thromboplastin time(Z=-3.026,P<0.05),prothrombin time(Z=-2.450,P<0.05),international normalized ratio(Z=2.779,P<0.05),and the proportion of moderate esophageal varices(χ2=4.273,P<0.05).During hospitalization,35 patients experienced new or aggravated ascites(18 with cardiac dysfunction and 17 without cardiac dysfunction),6 patients experienced new gastroesophageal variceal bleeding,and 9 patients experienced new or aggravated hepatic encephalopathy(3 with cardiac dysfunction and 6 without cardiac dysfunction).Jaundice was the most common decompensation event upon admission,and electrophysiological abnormalities were the most common electrocardiogram findings upon admission.During the 90-day follow-up period,30 individuals(12 with cardiac dysfunction and 18 without cardia dysfunction)died.The logistic regression analysis showed that age(odds ratio[OR]=1.075,95%confidence interval[CI]:1.033-1.119,P<0.001),N-terminal pro-B-type natriuretic peptide(NT-proBNP,OR=0.996,95%CI:0.992-0.999,P=0.016),and mild/moderate ascites(OR=0.270,95%CI:0.092-0.789,P=0.017)were independent predictive factors for cirrhotic cardiomyopathy.Conclusion Timely attention should be paid to elderly patients with decompensated liver cirrhosis and diastolic heart dysfunction who have a decline in NT-proBNP and mild to moderate ascites.Symptomatic treatment such as diuretics may improve diastolic heart dysfunction.
5.Non-invasive evaluation and prediction of portal hypertension: focusing on disease progression and outcome
Peishuang XU ; Mingchen WANG ; Jinjun CHEN ; Haiyu WANG
Chinese Journal of Hepatology 2025;33(10):928-933
Portal hypertension is a major complication of cirrhosis. The current gold standard for diagnosis is the hepatic venous pressure gradient, but it possesses limitations such as invasiveness. In recent years, non-invasive tests have made significant progress in terms of evaluating and prognostication of portal hypertension. This article reviews the diagnostic value and related research advancements of different non-invasive tests in assessing portal hypertension in patients with cirrhosis.
6.Characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction
Yichen YAO ; Haiyu WANG ; Lin DAI ; Qian WANG ; Ranran XI ; Junting WAN ; Jinjun CHEN
Journal of Clinical Hepatology 2025;41(8):1571-1578
Objective To retrospectively study the characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction,and to inform the clinical diagnosis and treatment of decompensated liver cirrhosis.Methods We retrospectively analyzed the clinical data of patients with liver cirrhosis and diastolic heart dysfunction admitted to Nanfang Hospital of Southern Medical University from April 1,2019 to July 31,2023.The patients were divided into compensated cirrhosis group(n=37)and decompensated cirrhosis group(n=226),and those with decompensated cirrhosis were further divided into subgroups of patients with heart dysfunction(n=84)and patients without heart dysfunction(n=142).We compared two groups using the independent samples t-test and Mann-Whitney U test for continuous data in normal distribution and data in skewed distribution,respectively;compared multiple groups using the Kruskal-Wallis H test,with subsequent paired comparisons using the Wilcoxon test;compared categorical data between two groups using the chi-square test or corrected chi-square test;identified the factors affecting patient survival using a Logistic regression model;and plotted Kaplan-Meier survival curves,with inter-group comparisons using the log-rank test.Results A total of 263 eligible patients were ultimately included,among whom 226 patients were diagnosed with decompensated liver cirrhosis(84 patients with diastolic dysfunction).Between the diastolic dysfunction group and non-diastolic dysfunction group,significant differences were detected in age(t=-4.566,P<0.05),activated partial thromboplastin time(Z=-3.026,P<0.05),prothrombin time(Z=-2.450,P<0.05),international normalized ratio(Z=2.779,P<0.05),and the proportion of moderate esophageal varices(χ2=4.273,P<0.05).During hospitalization,35 patients experienced new or aggravated ascites(18 with cardiac dysfunction and 17 without cardiac dysfunction),6 patients experienced new gastroesophageal variceal bleeding,and 9 patients experienced new or aggravated hepatic encephalopathy(3 with cardiac dysfunction and 6 without cardiac dysfunction).Jaundice was the most common decompensation event upon admission,and electrophysiological abnormalities were the most common electrocardiogram findings upon admission.During the 90-day follow-up period,30 individuals(12 with cardiac dysfunction and 18 without cardia dysfunction)died.The logistic regression analysis showed that age(odds ratio[OR]=1.075,95%confidence interval[CI]:1.033-1.119,P<0.001),N-terminal pro-B-type natriuretic peptide(NT-proBNP,OR=0.996,95%CI:0.992-0.999,P=0.016),and mild/moderate ascites(OR=0.270,95%CI:0.092-0.789,P=0.017)were independent predictive factors for cirrhotic cardiomyopathy.Conclusion Timely attention should be paid to elderly patients with decompensated liver cirrhosis and diastolic heart dysfunction who have a decline in NT-proBNP and mild to moderate ascites.Symptomatic treatment such as diuretics may improve diastolic heart dysfunction.
7.Non-invasive evaluation and prediction of portal hypertension: focusing on disease progression and outcome
Peishuang XU ; Mingchen WANG ; Jinjun CHEN ; Haiyu WANG
Chinese Journal of Hepatology 2025;33(10):928-933
Portal hypertension is a major complication of cirrhosis. The current gold standard for diagnosis is the hepatic venous pressure gradient, but it possesses limitations such as invasiveness. In recent years, non-invasive tests have made significant progress in terms of evaluating and prognostication of portal hypertension. This article reviews the diagnostic value and related research advancements of different non-invasive tests in assessing portal hypertension in patients with cirrhosis.
8.Value of urinary liver fatty acid-binding protein in predicting the short-term prognosis of patients with acute-on-chronic liver failure
Hualan WU ; Changze HONG ; Xiuhua JIANG ; Jinjun CHEN
Journal of Clinical Hepatology 2024;40(8):1639-1645
Objective To investigate the value of liver fatty acid-binding protein(L-FABP)in predicting the severity and short-term prognosis of patients with acute-on-chronic liver failure(ACLF).Methods A total of 149 patients with ACLF were selected from a prospective multicenter cohort assessing the platelet function of ACLF patients,and according to the 28-day prognosis after admission,they were divided into survival group with 97 patients and death group with 52 patients.The patients were analyzed in terms of sex,age,etiology,and blood routine,biochemical parameters,and organ failure status within 24 hours after admission,and the level of L-FABP in urine and blood was measured.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman test was used to evaluate the correlation between urinary L-FABP and indicators for liver failure.The receiver operating characteristic(ROC)curve was plotted to assess the value of CLIF-OFs,MELD score,and urinary L-FABP in predicting the short-term prognosis of ACLF patients;the Kaplan-Meier analysis was used to evaluate short-term mortality in the high urinary L-FABP group and the low urinary L-FABP group;the Cox proportional hazards model was used to investigate the association of each factor with the short-term prognosis of ACLF.Results There were significant differences between the two groups in white blood cell count,serum total bilirubin(TBil),international normalized ratio,CLIF-OFs,MELD score,urinary L-FABP level,and the proportion of patients with cerebral failure,liver failure,coagulation failure,renal failure,or respiratory failure(all P<0.05).The Spearman correlation analysis showed that urinary L-FABP was significantly positively correlated with serum TBil(r=0.225,P=0.006).Urinary L-FABP level had an area under the ROC curve of 0.804(95%confidence interval[CI]:0.729-0.865,P<0.001)and a cut-off value of 4.779 μg/dL,with a sensitivity of 73.08%,a specificity of 73.91%,and a Youden index of 0.469 9.The Kaplan-Meier survival analysis showed that compared with the low urinary L-FABP group(urinary L-FABP≤4.779 μg/dL),the high urinary L-FABP group(urinary L-FABP>4.779 μg/dL)had a significantly lower 28-day survival rate(P<0.001).The Cox proportional hazards model analysis showed that serum TBil(hazard ratio[HR]=1.003,95%CI:1.001-1.004,P<0.05),CLIF-OFs(HR=2.283,95%CI:1.814-2.873,P<0.05),and high urinary L-FABP level(HR=4.568,95%CI:2.424-8.608,P<0.05)were independent risk factors for the short-term prognosis of ACLF.Conclusion High urinary L-FABP level can be used as a clinical indicator for predicting the short-term prognosis of ACLF,and further studies with larger sample sizes are needed to evaluate its predictive value.
9.Efficacy of transjugular intrahepatic portosystemic shunt in treatment of hepatocellular carcinoma comorbid with esophagogastric variceal bleeding
Xiang GAO ; Xiaofeng ZHANG ; Yimin CAO ; Jinjun CHEN ; Xiaoqin LUO
Journal of Clinical Hepatology 2024;40(10):2027-2033
Objective To investigate the efficacy of transjugular intrahepatic portosystemic shunt(TIPS)in preventing rebleeding in patients with hepatocellular carcinoma(HCC)comorbid with esophagogastric variceal bleeding and the influencing factors for prognosis.Methods A retrospective analysis was performed for the clinical data of 35 HCC patients comorbid with esophagogastric variceal bleeding who were admitted to Zengcheng Branch of Nanfang Hospital,Southern Medical University,and were treated with TIPS from July 2019 to April 2023.The Kaplan-Meier curve was used to assess rebleeding rate and survival rate after TIPS,and the Cox regression model was used to investigate the influencing factors for postoperative rebleeding and survival.Results The TIPS procedure was technically successful in all patients,with a median follow-up time of 16.4 months.During follow-up,11 patients(31.4%)experienced esophagogastric variceal rebleeding,with the 1-month,3-month,and 1-year rebleeding rates of 5.7%,17.1%,and 28.6%,respectively.White blood cell count(WBC)(risk ratio[HR]=1.31,95%confidence interval[CI]:1.04-1.64,P=0.021),number of tumors≥3(HR=35.68,95%CI:1.74-733.79,P=0.021),and portal pressure gradient before TIPS(HR=0.85,95%CI:0.73-0.99,P=0.032)were independent predictive factors for rebleeding after TIPS.Shunt dysfunction was observed in 5 patients after surgery.A total of 19 patients died during follow-up,with a median survival time of 9.6 months.Portal vein tumor thrombosis(PVTT)(HR=7.04,95%CI:1.31-37.78,P=0.023),total bilirubin(TBil)(HR=1.02,95%CI:1.00-1.03,P=0.042),and serum albumin(HR=0.82,95%CI:0.72-0.94,P=0.004)were independent predictive factors for survival after TIPS.Conclusion TIPS procedure can be used as a therapeutic option to prevent esophagogastric variceal rebleeding in patients with HCC.Patients with a relatively high level of WBC or TBil or those with PVTT tend to have a poorer prognosis,and the application of TIPS treatment in such patients should be determined with caution.
10.Effects of catalpol on H2O2-induced osteoblast injury and its mechanism
Bo DUAN ; Lichuan CHEN ; Zhiyi MA ; Zhao YU ; Jing LIU ; Jinjun WANG
China Pharmacy 2024;35(10):1220-1225
OBJECTIVE To investigate the effects of catalpol on H2O2-induced osteoblast injury and its mechanism. METHODS The osteoblasts MC3T3-E1 were separated into control group, model group, empty group (transfected with empty plasmid), catalpol group (100 μmol/L), catalpol+forkhead box O3 (FoxO3) overexpression group (100 μmol/L catalpol+ transfected with FoxO3 overexpression plasmid). After catalpol treatment and transfection, except for control group, other groups were induced with H2O2 to establish osteoblast oxidative stress model. The cell viability, apoptotic rate, alkaline phosphatase (ALP) activity, optical density (OD) value of calcium nodule, mean fluorescence intensity (MFI) of reactive oxygen species (ROS), antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT)], the levels of inflammatory factors [interleukin-6 (IL-6), IL-1β], and the expressions of FoxO3/Wnt/β-catenin signaling pathway-related proteins were detected in each group. RESULTS Compared with the control group, the cell viability, ALP activity, OD value of calcium nodule, activities of antioxidant enzyme, and the protein expressions of Wnt and β-catenin were decreased significantly in the model group, while apoptotic rate, MFI levels of ROS, inflammatory factor levels and the protein expression of FoxO3 were all increased significantly (P<0.05). Compared with the model group, above indicators of the empty group had no significant change (P>0.05), while those of catalpol group were reversed significantly (P<0.05). Compared with the catalpol group, the reversal effect of the changes in the above indicators was significantly weakened in the catalpol+FoxO3 overexpression group cells (P<0.05). CONCLUSIONS Catalpol can activate Wnt/β-catenin signaling pathway by down-regulating FoxO3, thereby inhibiting H2O2-induced MC3T3-E1 oxidative stress and inflammation reaction, enhancing cell viability and osteogenic differentiation activity, and alleviating apoptosis injury.

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