In 2025， European Association for the Study of the Liver published the clinical practice guidelines on vascular diseases of the liver. The guidelines comprehensively elaborate on the vascular diseases of the liver from the aspects of risk factors， diagnosis， and treatment strategies， in order to provide guidance for the management of patients with these conditions based on the best evidence available. This article gives an excerpt of the recommendations and guidance statements in the clinical practice guidelines.

Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

The Baveno Cooperation is a consortium of internationally renowned experts committed to setting standards for the clinical management of patients with advanced chronic liver disease, with a particular emphasis on complications related to portal hypertension. Updated every five years and endorsed by major scientific societies, the Baveno recommendations have significantly influenced clinical practice and improved patient outcomes worldwide. The latest Baveno consensus, Baveno VII, provided a series of recommendations that have shifted our understanding of chronic liver disease and portal hypertension and profoundly shaped clinical practice. However, many areas of research remain to be explored in the short to intermediate term to enable a more personalized medicine approach. This review highlights some of the most relevant advancements introduced in Baveno VII and discusses future challenges.
Hypertension, Portal/therapy* ; Humans

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the correlation between the eosinophil percentage and prognosis in patients with sepsis after intensive care unit(ICU)admission.Methods A retrospec-tive cohort study design was employed,data from adult patients with sepsis or septic shock who were hospitalized for the first time and admitted to the ICU for the first time from the MIMIC-Ⅳ database(version 2.2)were selected.Patients were grouped according to differed eosinophil percentage(＜0.4％and≥0.4％),and the correlation between eosinophil percentage＜0.4％and prognostic out-comes was analyzed.Results A total of 616 patients were included.On the first day after ICU ad-mission,an eosinophil percentage＜0.4％was not significantly associated with prognosis;on the sec-ond day after ICU admission,patients with an eosinophil percentage＜0.4％exhibited a significantly increased 28-day mortality rate(HR=1.572,95％CI,1.119 to 2.208)and in-hospital mortality rate(HR=1.634,95％CI,1.137 to 2.349);on the third day after ICU admission,patients with an eosinophil percentage＜0.4％demonstrated significantly increased 28-day mortality rate(HR=2.072,95％CI,1.482 to 2.896),ICU mortality rate(HR=2.033,95％CI,1.296 to 3.188),and in-hospital mortality rate(HR=2.193,95％CI,1.533 to 3.136).Patients with eosinophil percentages＜0.4％on both the second day and the third day after ICU admission had the worst prog-nosis,with a significantly increased 28-day mortality rate(HR=2.271,95％CI,1.393 to 3.785).Conclusion The eosinophil percentages on the second day and the third day after ICU admission in patients with sepsis are closely correlated with prognosis,particularly aneosinophil percentage＜0.4％on the third day,which is significantly associated with a higher mortality rate.

Objective To explore the effect of A.muciniphila gavage on intestinal microbiota and gut-brain interaction disorders(DGBIs)in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder(HAND).Methods Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-,9-,and 12-month-old wild-type(WT)mice and gp120tg transgenic mice.The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage(2×108 CFU/mouse)for 6 weeks.After the treatment,immunohistochemistry,ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins,MBP and IL-1β,eosinophil infiltration,serum lipopolysaccharide(LPS)levels,and colonic expressions of occludin,ZO-1,IL-10,TNF-α and INF-γ mRNA.Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.Results Compared with WT mice,the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus,increased serum LPS levels and decreased colonic expression of glycosylated mucin.A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight.The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β,INF-γ and IL-1β levels and obviously lowered IL-10 level;all these changes were significantly mitigated by A.muciniphila gavage,which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.Conclusion The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice.The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes,and A.muciniphila gavage can reduce intestinal barrier injury,colonic inflammation and eosinophil activation,cognitive impairment and brain neuron injury in these mice.

Portal vein thrombosis(PVT)is a common and severe complication in patients with liver cirrhosis,and alterations in portal hemodynamics are closely associated with the development of PVT.The presence of large spontaneous splenorenal shunt(SSRS)may lead to reductions in portal vein perfusion and blood flow velocity,which may compromise the anticoagulant effect on PVT.This article reports the treatment strategies of SSRS embolization combined with anticoagulant therapy that help to achieve complete recanalization of the portal vein;however,high-quality clinical studies are still needed to further validate and support the effectiveness of this strategy.

Objective To explore the mechanism through which dexmedetomidine(Dex)alleviates doxorubicin(Adr)-induced myo-cardial injury via regulating nuclear factor κB(NF-κB)expression.Methods Sprague-Dawley rats were divided into control,Adr,and Adr+Dex groups.Theirs hearts were harvested for hematoxylin and eosin(HE)staining,immunohistochemical staining,real-time polymerase chain reaction(PCR),and Western blotting anlyses.The rat primary cardiomyocytes,breast cancer cell line MDA-MB-23,lung cancer cell line H226,gastric cancer cell line AGS,and bladder cancer cell line 5637 were cultured and divided into control,Adr,Adr+Dex,Dex,and Adr+Dex+NF-κBi groups.CCK-8 and immunofluorescence staining were performed to detect the reactive oxygen species(ROS)contents.Results The myocardial arrangement of the rats in the Adr group was disordered,myocardial cell activity was lower,the mitochondrial membrane potential was lower,ROS production was higher,and NF-κB mRNA and protein contents were sub-stantially lower than those in the control group.The cardiomyocyte morphology was improved,cell activity was higher,mitochondrial mem-brane potential was increased,ROS production decreased,and NF-κB expression significantly increased in the Adr+Dex group compared with those in the control group.The mitochondrial membrane potential in the Adr+Dex+NF-κBi group was lower,and ROS generation was increased compared with the control group.The activity of the tumor cells in the Adr group was lower,and no statistically significant diffe-rences were found compared with that in the Adr+Dex group.Conclusion Treatment with Dex may not affect the chemotherapeutic effects of Adr.Dex administration may increase the myocardial mitochondrial membrane potential and reduce ROS generation by regu-lating NF-κB levels,thereby reducing Adr-induced myocardial damage.