MASLD development: From molecular pathogenesis toward therapeutic strategies.

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.

Inhibition of Cyclooxygenase-2 Upregulates the Nuclear Factor Erythroid 2-related Factor 2 Signaling Pathway to Mitigate Hepatocyte Ferroptosis in Chronic Liver Injury.

Background And Aims: Ferroptosis plays an essential role in chronic liver diseases, and cyclooxygenase-2 (COX-2) affects liver fibrosis through multiple mechanisms. However, research on COX-2 regulation of ferroptosis in chronic liver injury remains limited. This study aimed to investigate whether and how COX-2 regulates ferroptosis in chronic liver injury.

Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial.

Background: There is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP).

Objective: We aimed to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety.

Design: In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18-75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group.

Benefits of TIPS for Patients With Large Ascites Preceding Recurrent or Refractory ascites: A Multicenter Cohort Study.

Background And Aim: Patients with recurrent or refractory ascites can benefit from transjugular intrahepatic portosystemic shunt (TIPS). However, the value of TIPS for patients with large ascites remains unclear.

Methods: This retrospective multicenter study included patients who underwent TIPS or medicine plus large-volume paracentesis (medicine + LVP) for ascites between January 2014 and December 2022 at five centers.

Post-TIPS Overt Hepatic Encephalopathy Increases Long-Term but Not Short-Term Mortality in Cirrhotic Patients With Variceal Bleeding: A Large-Scale, Multicenter Real-World Study.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure for managing portal hypertension in cirrhotic patients, but the impact of post-TIPS overt hepatic encephalopathy (OHE) on survival remains controversial. While its effect on short-term survival is well-documented, its long-term implications remain unclear.

Aims: This study aims to investigate the long-term impact of post-TIPS OHE on mortality in cirrhotic patients for variceal bleeding, focusing on the timing and predictive value of OHE beyond the first year post-TIPS.

Causal associations of immunophenotypes with metabolic dysfunction-associated fatty liver disease and mediating pathways: a Mendelian randomization study.

Background: Increasing evidence suggests that immunophenotypes play a crucial role in Metabolic dysfunction-associated fatty liver disease (MAFLD), but the specific immunophenotypes contributing to its pathogenesis remain unclear.

Objectives: This study aimed to elucidate the causal associations between immunophenotypes and MAFLD and identify the underlying mediation pathways involved.

Design: Mendelian randomization (MR) study.

Association between proton pump inhibitors and dementia risk: a Mendelian randomization study.

Numerous observational studies suggest associations between proton pump inhibitors (PPIs) and dementia, but causal relationships remain uncertain. Using large-scale genome-wide association study (GWAS) data, we performed univariable Mendelian randomization (UVMR) analysis to assess the causality between five PPI types, and all-cause dementia and its five subtypes. Confounders were controlled through multivariable MR (MVMR) analysis to isolate PPIs' direct effects on dementia.

Optimal threshold of portal pressure gradient for patients with ascites after covered TIPS: a multicentre cohort study.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is recommended for treating recurrent and refractory ascites. However, determining the target portal pressure gradient (PPG) has been inconclusive. This multicentre cohort study explored the post-TIPS PPG potential range associated with improving survival.

Activatable fluorescent probes for atherosclerosis theranostics.

The onset of atherosclerosis (AS) is insidious, and early stage patients have atypical clinical symptoms. After being diagnosed in late stage, it is often prone to sudden and fatal cardiovascular events. Therefore, it is highly desirable to develop precise and efficient diagnosis and therapy strategies of AS.

Dual-/multi-organelle-targeted AIE probes associated with oxidative stress for biomedical applications.

monitoring of biological processes between different organelles upon oxidative stress is one of the most important research hotspots. Fluorescence imaging is especially suitable for biomedical applications due to its distinct advantages of high spatiotemporal resolution, high sensitivity, non-invasiveness, and monitoring capabilities. However, most fluorescent probes can only achieve light-up imaging of single organelles, thus the combined use of two or more probes is usually required for monitoring biological processes between organelles, which can suffer from tedious staining and washing procedures, increased cytotoxicity and poor photostability.

Chinese guidelines on the management of ascites in cirrhosis : Chinese Society of Hepatology, Chinese Medical Association.

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as "Guidelines on the Management of Ascites in Cirrhosis." This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

Liver Cell Mitophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. MASLD and its advanced-stage liver fibrosis and cirrhosis are the leading causes of liver failure and liver-related death worldwide. Mitochondria are crucial organelles in liver cells for energy generation and the oxidative metabolism of fatty acids and carbohydrates.

Angiocrine signaling in sinusoidal homeostasis and liver diseases.

The hepatic sinusoids are composed of liver sinusoidal endothelial cells (LSECs), which are surrounded by hepatic stellate cells (HSCs) and contain liver-resident macrophages called Kupffer cells, and other patrolling immune cells. All these cells communicate with each other and with hepatocytes to maintain sinusoidal homeostasis and a spectrum of hepatic functions under healthy conditions. Sinusoidal homeostasis is disrupted by metabolites, toxins, viruses, and other pathological factors, leading to liver injury, chronic liver diseases, and cirrhosis.

Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

Background & Aims: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs.

Methods: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers.

Recent developments in the management of ascites in cirrhosis.

In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long-term albumin infusion may improve survival in patients with cirrhosis and ascites while beta-blockers may reduce ascites occurrence.

Guidelines for the Management of Esophagogastric Variceal Bleeding in Cirrhotic Portal Hypertension.

To standardize the diagnosis, treatment, and management of esophagogastric variceal bleeding (EVB) in patients with cirrhotic portal hypertension, the Chinese Society of Hepatology, the Chinese Society of Gastroenterology, and the Chinese Society of Digestive Endoscopy of the Chinese Medical Association brought together relevant experts, reviewed the latest national and international progress in clinical research on EVB in cirrhotic portal hypertension, and followed evidence-based medicine to update the Guidelines on the Management of EVB in Cirrhotic Portal Hypertension. The guidelines provide recommendations for the diagnosis, treatment, and management of EVB in cirrhotic portal hypertension and with the aim to improve the level of clinical treatment of EVB in patients with cirrhotic portal hypertension.

Remission of organ failure in patients with predicted severe acute pancreatitis treated by somatostation, octreotide and cyclooxygenase-2 inhibitors.

Background: /Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world.

ALOX5 acts as a key role in regulating the immune microenvironment in intrahepatic cholangiocarcinoma, recruiting tumor-associated macrophages through PI3K pathway.

Background: Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown.

Photoactivatable aggregation-induced emission luminogens based on photodehydrogenation reactions for biomedical applications.

The development of photoactivatable aggregation-induced emission (AIE) probes is one of the hotspots for bioimaging and imaging-guided precise disease therapy due to the distinct advantages of high spatiotemporal resolution, precise spatiotemporal controllability, and noninvasiveness of light. To design and develop novel photoactivatable AIE probes, functional groups based on photodehydrogenation reaction mechanisms are combined with the AIE-active skeleton. Here, the recent progress in biomedical applications of photoactivatable AIE probes based on photocyclodehydrogenation and photo-oxidative dehydrogenation reactions are summarized briefly.

The transcriptomic profile shows the protective effects of celecoxib on cirrhotic splenomegaly.

Background: Splenomegaly can exacerbate liver cirrhosis and portal hypertension. We have previously demonstrated that cyclooxygenase-2 (COX-2) inhibitor can attenuate cirrhotic splenomegaly. However, the mechanism of cirrhotic splenomegaly remains unclear, thus becoming the focus of the present study.

Disruption of cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis alleviates liver fibrosis.

B cells can promote liver fibrosis, but the mechanism of B cell infiltration and therapy against culprit B cells are lacking. We postulated that the disruption of cholangiocyte-B-cell crosstalk could attenuate liver fibrosis by blocking the CXCL12-CXCR4 axis via a cyclooxygenase-2-independent effect of celecoxib. In wild-type mice subjected to thioacetamide, celecoxib ameliorated lymphocytic infiltration and liver fibrosis.

A narrative review of acute pancreatitis-induced splanchnic vein thrombosis: from pathogenesis to clinical management.

Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management. In this study, we reviewed the latest academic publications in APISVT, and discussed its pathogenesis, clinical presentation, adverse outcome and treatment, especially focused on the role of anticoagulant therapy.

Incidence, prevalence, and comorbidities of chronic pancreatitis: A 7-year population-based study.

Background: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to reduced quality of life and shortened life expectancy. Population-based estimates of the incidence, prevalence, and comorbidities of CP in China are scarce.

Aim: To characterize the incidence, prevalence, and comorbidities of CP in Sichuan Province, China, with population-based data.