Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

Background: Apolipoprotein A-I (ApoA-I) is a key cardioprotective lipoprotein. Nevertheless, it remains unclear how ApoA-I relates to ischemic risk across glucose metabolism statuses in patients with coronary artery disease (CAD). This study investigated whether glucose metabolism status influences the association between ApoA-I and ischemic risk in CAD patients. Methods: This cohort study included 10,724 consecutive CAD patients undergoing percutaneous coronary intervention, who were classified into diabetes mellitus (DM), pre-DM, and normal glucose regulation (NGR) groups. The primary clinical endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, revascularization, and stroke. Results: Of the 10,232 patients ultimately included, 2,139 (20.9%) experienced MACCE over 5 years. A significant interaction was observed between ApoA-I levels and glucose metabolism status (P for interaction=0.041). In the DM group, an L-shaped association between ApoA-I and MACCE was found, with lower ApoA-I levels linked to a higher risk of MACCE (P for non-linearity= 0.044). Multivariate Cox regression analysis showed that patients in the lowest quintile of ApoA-I had a 1.327-fold increased risk of MACCE compared to those at the lowest risk (hazard ratio, 1.327; 95% confidence interval, 1.097 to 1.604). However, no significant association was observed in the pre-DM or NGR groups (both P>0.05). Conclusion This large-scale, 5-year follow-up study is the first to demonstrate that lower ApoA-I levels are associated with increased MACCE risk in CAD patients with DM, highlighting the potential value of ApoA-I in risk stratification and as a therapeutic target.

Hypomyelinating leukodystrophies (HLDs) are a group of neurodegenerative diseases characterized by decreased myelination in the central nervous system, with diverse clinical manifestations like psychomotor retardation and dyskinesia.Some HLDs patients have epilepsy, microcephaly and other clinical manifestations.At present, there is no specific treatment of HLDs, and the prognosis is usually poor.At present, with the wide application of gene screening in clinical practice, many pathogenic genes related to HLDs have been found.It is particularly important to clarify the pathogenesis and clinical phenotypic changes of HLDs.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.