As a key receptor for immune regulation， triggering receptor expressed on myeloid cells 2 （TREM2） plays an important role in the development and progression of liver diseases， but its specific mechanisms and regulatory strategies in different types and stages of liver diseases remain to be systematically elucidated. This article systematically reviews the molecular characteristics and signaling pathways of TREM2， elaborates on the multiple functions of TREM2⁺ macrophages in lipid metabolism， phagocytic function， inflammatory response， and fibrosis， and analyzes the dynamic and bidirectional roles of TREM2 in different liver diseases. Targeting the TREM2 signaling axis is expected to become a new strategy for regulating the hepatic immune microenvironment and intervening in disease progression.

Small intestinal bacterial overgrowth （SIBO） is significantly more prevalent in patients with liver cirrhosis. Recent studies indicate that SIBO is not merely a concomitant phenomenon but a key driver of cirrhosis progression via the “gut-liver axis” mechanism. This review innovatively proposes a “microbiota-immunity-fibrosis” pathological positive feedback loop model， systematically elucidating the sequential pathological process through which SIBO drives disease progression via multiple mechanisms—including disruption of intestinal barrier function， facilitation of bacterial and endotoxin translocation， induction of systemic inflammatory responses， and acceleration of hepatic fibrosis. Furthermore， it provides a systematic evaluation of the clinical application value and limitations of current SIBO-targeted therapeutic strategies， such as antibiotic therapy， microbial modulation， herbal medicine interventions， and dietary therapies. This work aims to establish a theoretical foundation and identify future research directions for the development of multi-targeted and personalized comprehensive treatment strategies.

Objective To explore the application of the Autoregressive Integrated Moving Average (ARIMA) model in predicting the number of reported hepatitis E cases in Yunnan Province，to use this model to predict the incidence trend of hepatitis E, and to provide reference for the scientific prevention and control of hepatitis E. Methods Monthly reported cases of hepatitis E in Yunnan Province from 2012 to 2021 were collected. The ARIMA model was established using SPSS 27.0, and the model was validated and parameters were optimized with data from January 2022 to December 2022. The optimal fitting model was used to predict the incidence of hepatitis E in 2023. Results Hepatitis E incidence in Yunnan Province showed a certain seasonal distribution, with most cases concentrated from March to August. All parameters of ARIMA(3,1,4)(1,1,1)₁₂ passed statistical tests. The Ljung-Box test showed statistic Q =10.050, P = 0.346, residual sequence was a white noise sequence, and goodness-of-fit index stationary R² was 0.591. The model extrapolation effect was verified with 2022 data, and MAPE was 14.747, indicating that the model extrapolation effect was effective. The number of hepatitis E cases in Yunnan Province in 2023 was expected to be 1,086. Conclusion The ARIMA (3,1,4)(1,1,1)₁₂ model shows good fitting performance for hepatitis E cases in Yunnan Province and can effectively predict short-term disease trends, providing a theoretical basis for formulating prevention and control measures for hepatitis E.

With the progression of liver cirrhosis， patients often develop sarcopenia and lipid metabolism disorders， and the complex interaction between p sarcopenia and lipid metabolism disorders not only promotes the progression of liver cirrhosis， but also affects the prognosis and quality of life of patients. As an effective intervention for alleviating complications associated with liver cirrhosis， transjugular intrahepatic portosystemic shunt （TIPS） can improve sarcopenia to a certain degree by improving hepatic hemodynamics and reducing portal venous pressure. In addition， there might be varying degrees of changes in blood lipid levels after TIPS， which may be closely associated with the recovery of liver metabolic function and the alterations in hemodynamics. This article introduces the association between liver cirrhosis， sarcopenia， and lipid metabolism disorders， elaborates on the effect of TIPS on sarcopenia and abnormal lipid metabolism， and discusses related mechanism and clinical significance， in order to provide a theoretical basis for clinical treatment.

The grade of histological severity is a determining factor to evaluate the prognosis and survival rate in primary biliary cholangitis (PBC). However, liver biopsy is limited by sampling error, invasiveness, high cost, and poor compliance. Therefore, in order to overcome the limitations of liver biopsy, some non-invasive evaluation methods have been studied and applied to evaluate the progression of liver fibrosis in PBC. The prognostic score can be calculated using routine laboratory test results obtained at the time of diagnosis, which are characterized by their simplicity, affordability, ease of acquisition, and superior reproducibility. Recent studies have reported that the prognostic score can be employed as a non-invasive liver fibrosis model to diagnose the liver fibrosis stage in PBC and predict the transplant-free survival rate, in addition to being used to evaluate the patient prognosis and transplant-free survival (TFS). This paper reviews, summarizes, and explores the research progress of different prognostic scores as non-invasive liver fibrosis models via their diagnostic performance and predictive accuracy for PBC.

Lipoprotein X(LpX)is an atypical lipoprotein that abnormally accumulates in the plasma of patients with cholestatic liver disease,and it is also a major pathogenic factor for hypercholesterolemia.The formation of LpX is closely associated with the abnormal metabolism of free cholesterol,phospholipids,and other lipid components in bile.LpX cannot be cleared via the low-density lipoprotein receptor pathway and is mainly metabolized by the reticuloendothelial system.The abnormal accumulation of LpX is closely associated with various complications of cholestatic liver disease,including xanthoma and neuropathy.Although there is no significant correlation between the high level of LpX and the risk of atherosclerosis,the role of LpX in cholesterol metabolism disorders cannot be neglected.Due to the similarities in density and characteristics between LpX and low-density lipoprotein cholesterol,clinical testing may result in misdiagnosis and related treatment risks.Current studies mainly focus on the mechanisms of LpX formation,the clinical significance of LpX,related detection methods,and potential therapeutic strategies.Plasma exchange is considered the preferred treatment in the state of high LpX,while traditional lipid-lowering drugs have a limited effect on LpX.This article explores the formation and clearance mechanisms of LpX in cholestatic liver disease,along with its impact of cholestatic liver disease and related detection methods,in order to improve the understanding of the pathophysiology and clinical significance of LpX,provide new strategies for the management of cholestatic liver disease and its complications,and finally improve the prognosis of patients.

Objective To investigate the binding interaction between the calmodulin(CaM)mutant D130V and the IQ motif of the car-diac Cav1.2 channel.Methods The binding of mutant CaM-D130V to the IQ motif was predicted by fold recognition modeling,homology modeling,and protein docking.The plasmid was transformed into Escherichia coli BL-21 sensory cells via heat shock at 42 ℃ to induce the expression of glutathione S-transferase(GST)fusion protein.The protein was extracted by ultrasonic fragmentation and purified using GS-4B beads.PreScission protease was applied to remove the GST.SDS-PAGE was performed to detect the purity of protein.A GST pull-down assay was conducted to detect the interaction between CaM-D130V and IQ motif.Results Protein docking results showed that both CaM-WT and CaM-D130V could bind to the IQ motif of the cardiac Cav1.2 channel,but the binding sites of the mutant CaM-D130V to the IQ motif were reduced,and its binding conformation was changed compared with the CaM-WT,with decreased binding energy(|S|reduced from 48.086 6 kcal/mol to 47.309 5 kcal/mol).The GST pull-down assay indicated that the binding of CaM-D130V to IQ motif significantly decreased(P＜0.01),and the affinity was significantly reduced at 2 mmol/L Ca2+concentration compared with CaM-WT.Conclusion The reduced binding ability of CaM-D130V to the IQ motif of the cardiac Cav1.2 channel may contribute to functional alterations in the channel.These findings provide a theoretical basis for understanding the pathogenesis of CaM mutant-associated cardio-vascular diseases as well as targeted therapies.

Lipoprotein X(LpX)is an atypical lipoprotein that abnormally accumulates in the plasma of patients with cholestatic liver disease,and it is also a major pathogenic factor for hypercholesterolemia.The formation of LpX is closely associated with the abnormal metabolism of free cholesterol,phospholipids,and other lipid components in bile.LpX cannot be cleared via the low-density lipoprotein receptor pathway and is mainly metabolized by the reticuloendothelial system.The abnormal accumulation of LpX is closely associated with various complications of cholestatic liver disease,including xanthoma and neuropathy.Although there is no significant correlation between the high level of LpX and the risk of atherosclerosis,the role of LpX in cholesterol metabolism disorders cannot be neglected.Due to the similarities in density and characteristics between LpX and low-density lipoprotein cholesterol,clinical testing may result in misdiagnosis and related treatment risks.Current studies mainly focus on the mechanisms of LpX formation,the clinical significance of LpX,related detection methods,and potential therapeutic strategies.Plasma exchange is considered the preferred treatment in the state of high LpX,while traditional lipid-lowering drugs have a limited effect on LpX.This article explores the formation and clearance mechanisms of LpX in cholestatic liver disease,along with its impact of cholestatic liver disease and related detection methods,in order to improve the understanding of the pathophysiology and clinical significance of LpX,provide new strategies for the management of cholestatic liver disease and its complications,and finally improve the prognosis of patients.

Objective To investigate the binding interaction between the calmodulin(CaM)mutant D130V and the IQ motif of the car-diac Cav1.2 channel.Methods The binding of mutant CaM-D130V to the IQ motif was predicted by fold recognition modeling,homology modeling,and protein docking.The plasmid was transformed into Escherichia coli BL-21 sensory cells via heat shock at 42 ℃ to induce the expression of glutathione S-transferase(GST)fusion protein.The protein was extracted by ultrasonic fragmentation and purified using GS-4B beads.PreScission protease was applied to remove the GST.SDS-PAGE was performed to detect the purity of protein.A GST pull-down assay was conducted to detect the interaction between CaM-D130V and IQ motif.Results Protein docking results showed that both CaM-WT and CaM-D130V could bind to the IQ motif of the cardiac Cav1.2 channel,but the binding sites of the mutant CaM-D130V to the IQ motif were reduced,and its binding conformation was changed compared with the CaM-WT,with decreased binding energy(|S|reduced from 48.086 6 kcal/mol to 47.309 5 kcal/mol).The GST pull-down assay indicated that the binding of CaM-D130V to IQ motif significantly decreased(P＜0.01),and the affinity was significantly reduced at 2 mmol/L Ca2+concentration compared with CaM-WT.Conclusion The reduced binding ability of CaM-D130V to the IQ motif of the cardiac Cav1.2 channel may contribute to functional alterations in the channel.These findings provide a theoretical basis for understanding the pathogenesis of CaM mutant-associated cardio-vascular diseases as well as targeted therapies.

The grade of histological severity is a determining factor to evaluate the prognosis and survival rate in primary biliary cholangitis (PBC). However, liver biopsy is limited by sampling error, invasiveness, high cost, and poor compliance. Therefore, in order to overcome the limitations of liver biopsy, some non-invasive evaluation methods have been studied and applied to evaluate the progression of liver fibrosis in PBC. The prognostic score can be calculated using routine laboratory test results obtained at the time of diagnosis, which are characterized by their simplicity, affordability, ease of acquisition, and superior reproducibility. Recent studies have reported that the prognostic score can be employed as a non-invasive liver fibrosis model to diagnose the liver fibrosis stage in PBC and predict the transplant-free survival rate, in addition to being used to evaluate the patient prognosis and transplant-free survival (TFS). This paper reviews, summarizes, and explores the research progress of different prognostic scores as non-invasive liver fibrosis models via their diagnostic performance and predictive accuracy for PBC.