Pancreatic cancer-derived extracellular vesicles remodel the tumor microenvironment and enhance chemoresistance by delivering KRAS protein to cancer-associated fibroblasts.

KRAS mutations are instrumental in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the efficacy of direct targeting of KRAS mutations to inhibit tumor development remains doubtful. It is therefore necessary to gain a deeper insight into the mechanism in which KRAS mutations influence the effectiveness of clinical treatments.

Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial.

Background Aims: The role of adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in HCC patients.

Approach Results: In this randomized phase 3 trial, histologically confirmed HCC patients (AJCC TNM stage I and II) were randomly assigned (1:1) to adjuvant TACE or observation groups.

Biological and clinical role of TREM2 in liver diseases.

Liver diseases constitute a major health burden worldwide, accounting for more than 4% of all disease-related mortalities. While the incidence of viral hepatitis is expected to decrease, metabolic liver disorders are increasingly diagnosed. Liver pathology is diverse, with functional and molecular alterations in both parenchymal and mesenchymal cells, including immune cells.

Cancer immunotherapeutic challenges from autophagy-immune checkpoint reciprocal regulation.

Multiple strategies have been clinically employed as combination partners to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Although these combinations have demonstrated improved effectiveness in some instances, each presents its own limitations. Autophagy-targeting therapy offers several advantages when combined with ICIs, including enhanced tumor immunogenicity, reduced side effects, and broader applicability to diverse patient populations.

Chinese guidelines for minimally invasive donor hepatectomy in living donor liver transplantation (2024 edition).

Background: Minimally invasive surgeries are increasingly central to modern medicine, particularly in liver transplantation. These techniques, which offer reduced trauma, precise operations, minimal bleeding, and swift recovery, are, however, unevenly adopted across China. Only a limited number of centers routinely perform minimally invasive donor hepatectomies, indicating a significant imbalance in the development and application of these advanced procedures.

Systemic Treatment Followed by Radical Resection Combined with Intestinal Autotransplantation (RRCIA) for Locally Advanced Pancreatic Cancer: A Retrospectively Observational and Prospectively Validated Study.

Objective: The present study aimed to assess the efficacy of this approach and establish the criteria that identify LAPC patients who may achieve survival benefits from RRCIA.

Summary Background Data: Surgical resection for locally advanced pancreatic cancer (LAPC) remains challenging and associated with high morbidity and mortality, especially for surgery with major arterial reconstruction. We previously showed the feasibility and safety of Radical Resection Combined with Intestinal Autotransplantation (RRCIA) after systemic treatment.

Risk Factors, Manifestations, and Implications of Chyle Leak -Following Pancreatic Surgery: The Volume May Outweigh the Milky Appearance of the Drainage in a Chyle Leak.

Objective: To identify the risk factors, manifestations, and clinical implications of chyle leak (CL) after pancreatic surgery, and to reappraise the International Study Group for Pancreatic Surgery (ISGPS) definition and classification of CL.

Summary Background Data: The risk factors, clinical scenarios, and management of CL after pancreatic surgery remain controversial.

Methods: Data from patients who underwent pancreatic surgery between January 2019 and July 2023 were retrieved from an institutional database.

RAD51 plays critical roles in DNMT1-mediated maintenance methylation of genomic DNA by dually regulating the ubiquitin ligase UHRF1.

is related to the bacterial RecA protein and is best known for its role in homologous recombination-mediated repair of DNA damage. Here, we report an unexpected function of in the maintenance methylation of genomic DNA, a function that is separable from its role in homologous recombination. First, it acts as an inhibitor of the E3 ubiquitin ligase UHRF1.

Interfacial Engineering of Biocompatible Nanocapsules for Near-Infrared-Triggered Drug Release and Photothermal Therapy.

Chemotherapy is an effective option for cancer treatment. However, its clinical application is often limited by the severe side effects of chemical drugs. To overcome these limitations, a novel drug-loaded phase-change nanocapsule system is developed.

Vasopressin drives aberrant myeloid differentiation of hematopoietic stem cells, contributing to depression in mice.

Psychological stress is often linked to depression and can also impact the immune system, illustrating the interconnectedness of mental health and immune function. Hematopoietic stem cells (HSCs) can directly sense neuroendocrine signals in bone marrow and play a fundamental role in the maintenance of immune homeostasis. However, it is unclear how psychological stress impacts HSCs in depression.

TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.

Mechanical control is fundamental for cellular localization within a tissue, including for tumor-associated macrophages (TAMs). While the innate immune sensing pathways cGAS-STING and RLR-MAVS impact the pathogenesis and therapeutics of malignant diseases, their effects on cell residency and motility remain incompletely understood. Here, we uncovered that TBK1 kinase, activated by cGAS-STING or RLR-MAVS signaling in macrophages, directly phosphorylates and mobilizes Zyxin, a key regulator of actin dynamics.

Reprograming immunosuppressive microenvironment by eIF4G1 targeting to eradicate pancreatic ductal adenocarcinoma.

Current therapies against pancreatic ductal adenocarcinoma (PDAC) have limited clinical benefits owing to tumor heterogeneity and their unique immunosuppressive microenvironments. The eukaryotic initiation factor (eIF) 4F complex is involved in regulating translation and various downstream carcinogenic signaling pathways. We report that eIF4G1, one of the subunits of eIF4F, is overexpressed in cancer cells and cancer-associated fibroblasts, and this correlates with poor prognosis in patients with PDAC.

Microglial cGAS-STING signaling underlies glaucoma pathogenesis.

Characterized by progressive degeneration of retinal ganglion cells (RGCs) and vision loss, glaucoma is the primary cause of irreversible blindness, incurable and affecting over 78 million patients. However, pathogenic mechanisms leading to glaucoma-induced RGC loss are incompletely understood. Unexpectedly, we found that cGAS-STING (2'3'-cyclic GMP-AMP-stimulator of interferon genes) signaling, which surveils displaced double-stranded DNA (dsDNA) in the cytosol and initiates innate immune responses, was robustly activated during glaucoma in retinal microglia in distinct murine models.

A novel clinical data management platform for acute pancreatitis.

This study presents a multi-center clinical data management platform that facilitates unified and structured management of real-world data and serves as an ideal tool to enhance the quality and progress of clinical research related to severe acute pancreatitis (SAP). The use of the platform enables clinical teams to obtain safe, accurate, structurally unified, traceable, scene-clear, and fully functional real-world medical data in the diagnosis, treatment, and research of acute pancreatitis (AP).

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell.

Deciphering extracellular vesicles protein cargo in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents a significant therapeutic challenge as it is frequently diagnosed at advanced inoperable stages. Therefore, the development of a reliable screening tool for PDAC is crucial for effective prevention and treatment. Extracellular vesicles (EVs), characterized by their cup-shaped lipid bilayer structure and ubiquitous release from various cell types, offer notable advantages as an emerging liquid biopsy technique that is rapid, minimally invasive, easily sampled, and cost-effective.

The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis.

Background: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC.

Methods: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected.