1.Establishment and validation of a risk prediction model for 90-day mortality in patients with acute-on-chronic liver failure based on sarcopenia
Huina CHEN ; Ming KONG ; Siqi ZHANG ; Manman XU ; Yu CHEN ; Zhongping DUAN
Journal of Clinical Hepatology 2025;41(6):1135-1142
ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure (ACLF) based on sarcopenia and other clinical indicators, and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital, Capital Medical University, from January 2019 to January 2022 were enrolled, and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group, CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra (L3), and L3 skeletal muscle index (L3-SMI) was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors, and a nomogram was developed for presentation. The area under the ROC curve (AUC) was used to assess the predictive performance of the model, the calibration curve was used to assess the degree of calibration, and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR]=1.962, 95% confidence interval [CI]: 1.185 — 3.250, P=0.009), total bilirubin (HR=1.003, 95%CI: 1.002 — 1.005, P<0.001), international normalized ratio (HR=1.997, 95%CI: 1.674 — 2.382, P<0.001), and lactic acid (HR=1.382, 95%CI: 1.170 — 1.632, P<0.001) were included in the sarcopenia-ACLF model. In the training cohort, the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF (0.80 vs 0.73, Z=1.97, P=0.049). In the test cohort, the sarcopenia-ACLF model had a significantly larger AUC than MELD score (0.79 vs 0.69, Z=2.70, P=0.007) and MELD-Na score (0.79 vs 0.68, Z=2.92, P=0.004). The calibration curve showed that the model had good calibration ability, with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities, the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients, which provides support for clinical decision-making and helps to optimize treatment strategies.
2.Association between different regional fat distribution and total body bone mineral density in children and adolescents
CHEN Jingran, CHEN Manman, HE Huiming, LI Menglong, SUN Mengyang, HU Yifei
Chinese Journal of School Health 2025;46(7):1005-1008
Objective:
To analyze the association between each regional fat mass and total body bone mineral density (BMD) in children and adolescents aged 7-17 years in Beijing, so as to provide theoretical basis and practical guidance for implementing interventions.
Methods:
From September to December 2020, a stratified cluster random sampling method was used to select 1 423 children and adolescents aged 7-17 years in Tongzhou District, Beijing. Dual energy X-ray absorptiometry (DXA) was employed to measure regional body composition and total body BMD. Multiple linear regression was used to analyze the association between regional fat mass and total body BMD.
Results:
The median (interquartile range) fat mass values for total body, upper limbs, abdomen, hips, and thighs were 13.51(8.84, 19.21), 1.59(1.08, 2.23), 0.73(0.39, 1.29), 2.32(1.46, 3.26), 5.29(3.59, 7.21)kg, respectively. After adjusting for covariates, the results of multiple linear regression analysis showed that total body fat mass (β=0.010), abdominal fat mass (β=-0.100), and hip fat mass (β=0.104) were significant associations with total body BMD (all P<0.01). Sexstratified analysis revealed that in boys, total body fat mass (β=0.008) and hip fat mass (β=0.058) were positively associated with BMD, while thigh fat mass (β=-0.038) showed a negative association with total body BMD (all P<0.05). In girls, total body fat mass (β=0.013), hip fat mass (β=0.163), and thigh fat mass (β=0.023) were positively associated with total body BMD, whereas abdominal fat mass (β=-0.196) showed a negative association with total body BMD (all P<0.05). Among children and adolescents with body fat percentage below the standard range, within the standard range and above the standard range, total body fat masses were positively associated with total body BMD (β=0.021, 0.016, 0.015); among children and adolescents with body fat percentage within the standard range while upper limb (β=-0.042), abdominal (β=-0.067), and thigh fat mass (β=-0.018) showed negative associations with total body BMD, and hip fat mass demonstrated a positive association with total body BMD (β=0.082) (all P<0.05).
Conclusion
Regional fat distribution is associated with total body BMD in children and adolescents, with the nature of these associations varying by sex and body fat percentage.
3.Dynamic changes of prognostic scores and related clinical indicators in hepatitis B virus-related acute-on-chronic liver failure patients without underlying liver cirrhosis and their relationship with clinical outcomes
Wenling WANG ; Manman XU ; Yu WU ; Jiateng ZHANG ; Huaibin ZOU ; Yu CHEN
Journal of Clinical Hepatology 2025;41(9):1771-1778
ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients without liver cirrhosis, to clarify their association with outcomes, and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023, including prognostic scores and key biochemical indicators on Days 3, 7, 14, 21, and 28 of the disease course. According to the outcome of patients at 1 year, they were divided into death/liver transplantation group with 43 patients, liver cirrhosis group with 23 patients, and non-liver cirrhosis group with 88 patients, and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups; the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval (CI) were calculated for each indicator at difference time points; the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve; the 95%CI was visualized using the semi-transparent ribbon area, with the transparency parameter (α=0.2) optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes; likelihood ratio was used to evaluate the significance of the interaction effect between time and group, and in case of the significant interaction effect, the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy, MELD score, MELD-Na score, CLIF-C ACLF score, COSSH-ACLF Ⅱ score, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein, blood sodium, alanine aminotransferase, and procalcitonin at the baseline(all P0.05). The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR (TBil400 μmol/L, INR2.5), as well as a low level of platelet count (PLT) (100×10⁹/L). The non-liver cirrhosis group had rapid improvements in indicators, with TBil200 μmol/L, INR1.5, and PLT100×10⁹/L by day 28, while the liver cirrhosis group showed a trend of recovery, with TBil200 μmol/L, INR2.0, and PLT 100×10⁹/L on day 28, with significant global heterogeneity in the temporal trends of the above indicators across the three groups (all P0.01). ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year, individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5, TBil 200 μmol/L, and PLT 100×10⁹/L at day 28.
4.Interpretation of guideline for diagnosis and treatment of acute-on-chronic liver failure (2025 edition)
Manman XU ; Huaibin ZOU ; Zhongping DUAN ; Tao HAN ; Yu CHEN
Journal of Clinical Hepatology 2025;41(5):844-850
In 2025, Severe Liver Disease and Artificial Liver Group and Nutrition and Regeneration in End-Stage Liver Disease Group of Chinese Society of Hepatology, Chinese Medical Association, convened a panel of national experts to jointly develop China’s first guideline for the diagnosis and treatment of acute-on-chronic liver failure (ACLF). Based on the latest research findings and clinical practice in China and globally, this guideline establishes a standardized definition of ACLF and provide recommendations for its diagnosis, treatment, and clinical management. This article gives an interpretation of the key points in the guideline, in order to provide a reference for standardized diagnosis and treatment of ACLF.
5.Prognostic evaluation of liver transplantation for acute-on-chronic liver failure
Man LAI ; Manman XU ; Xin WANG ; Guangming LI ; Yu CHEN
Organ Transplantation 2025;16(3):482-488
Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function occurring on the basis of chronic liver disease, accompanied by failure of the liver and extrahepatic organs, and is associated with a high short-term mortality rate. Liver transplantation is the only curative treatment for patients with ACLF. However, the shortage of donor livers and limitations of the organ allocation system mean that only a minority of patients can receive transplants. The current organ allocation system based on the model for end-stage liver disease (MELD) score may underestimate the urgency of liver transplantation for ACLF patients. Therefore, it is urgent to develop better assessment tools to determine which ACLF patients are most likely to benefit from liver transplantation. This article reviews the current mainstream definitions of ACLF, the selection of candidates for liver transplantation in ACLF, and the prognostic scoring systems for liver transplantation in ACLF, both domestically and internationally, in order to provide a reference for the prognostic assessment of liver transplantation in ACLF patients.
6.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
7.Association of triglyceride glucose index and risk of incident hypertension: a prospective cohort study
Xi CHEN ; Manman WEI ; Zhengxun ZHANG ; Ge LIU ; Ruoshan WANG ; Xinyuan YOU ; Dongsheng HU ; Yang ZHAO
Chinese Journal of Cardiology 2024;52(4):413-419
Objective:To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults.Methods:A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk.Results:The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles ( Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 ( RR=1.11, 95% CI 1.01-1.22, P=0.023), TyG 8.6-8.9 ( RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 ( RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions:The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.
8.Unified consensus and evolution of the definition of acute-on-chronic liver failure:Seeking common ground while reserving differences
Journal of Clinical Hepatology 2024;40(11):2173-2176
The concept of acute-on-chronic liver failure(ACLF)has been introduced for nearly 30 years,and with extensive research on its pathogenesis,diagnostic criteria,and treatment strategies,related consensus statements and guidelines have been constantly updated in China and globally;however,there is still a lack of a unified definition of ACLF,and such differences in definition may inevitably hinder the application and implementation of various treatment methods,prognostic scoring systems,and clinical recommendations.In recent years,hepatology experts have continuously proposed methods to unify the definition of ACLF,seeking common ground while reserving differences and drawing on the strengths of various definitions,in order to achieve a more unified definition of ACLF.
9.Effect of Xiaoxuming decoction on OGD/R-induced synaptic plasticity in HT22 cells
Manman WANG ; Rui LAN ; Yong ZHANG ; Xueqin FU ; Xuhuan ZOU ; Weiwei WANG ; Hongyu LI ; Chen TANG ; Shuang LIU
Chinese Journal of Pathophysiology 2024;40(1):126-133
AIM:To explore the protective effect of Xiaoxuming decoction(XXMD)on synaptic plasticity in the context of cerebral ischemia-reperfusion injury following ischemic stroke.METHODS:An oxygen-glucose depriva-tion/reoxygenation(OGD/R)model was employed in vitro using mouse hippocampal neurons(HT22 cells)to simulate ischemia-reperfusion injury.Cell viability was assessed using a CCK-8 assay to determine the optimal XXMD concentra-tion.The HT22 cells were divided into two groups:control and model(OGD/R).Cellular morphological changes were ob-served using an inverted microscope.The levels of IL-1β,IL-6 and TNF-α in the supernatant were quantified by ELISA.Ultrastructural changes were examined by transmission electron microscopy.Immunofluorescence staining was used to de-tect neuron markers NeuN and synaptic proteins NF200 and MAP2.The protein levels of NF200 and MAP2 were analyzed by Western blot.RESULTS:The highest cell survival rate occurred at an XXMD concentration of 100 mg/L(P<0.05).Compared with control group,the cells in model group exhibited round shape and shrinkage,mitochondrial swelling or vacuolization,and a marked decrease in survival rate.There were significant increases in IL-1β,IL-6 and TNF-α levels(P<0.05).Immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2 were notably reduced(P<0.05).Treatment with XXMD improved cell morphology,ultrastructure and survival rate(P<0.05),and decreased in-flammatory factor levels(P<0.05).Compared with model group,the cells in OGD/R+XXMD group showed significantly increased immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2(P<0.05).CONCLUSION:Xiaoxuming decoction may mitigate OGD/R-induced injury,potentially by inhibiting inflammatory responses and enhanc-ing synaptic plasticity.
10.Research progress of berberine in the field of neuroprotection in ischemic stroke
Hongyu LI ; Rui LAN ; Manman WANG ; Weiwei WANG ; Yong ZHANG ; Chen TANG ; Shuang LIU
Chinese Journal of Comparative Medicine 2024;34(2):129-136
Berberine is a natural isoquinoline alkaloid that was initially used as a broad-spectrum antibacterial agent in clinical treatment of enteritis,peptic ulcers,chronic gastritis,pneumonia,and other diseases.In recent years,in-depth study of the pharmacological effects of berberine has provided increasing evidence that berberine has neuroprotective effects on ischemic stroke.In this review,we introduce the effect of berberine on risk factors of ischemic stroke and discuss the neuroprotective effects of berberine on various mechanisms of ischemic stroke in detail to provide a reference for clinical and basic research in this field.


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