The impact of restrictive blood transfusion on the safety of patients with esophageal varices after endoscopic variceal ligation: A single-center retrospective study.

An investigation was conducted to examine the impact of restrictive blood transfusion on the safety of early rebleeding following endoscopic variceal ligation (EVL) in patients with liver cirrhosis. Data were collected from patients with cirrhosis and esophageal varices who underwent EVL at the Affiliated Hospital of North Sichuan Medical College between September 2021 and March 2023. Clinical information, including serum albumin levels, hemoglobin (Hb) levels, liver function classification, and the occurrence of early rebleeding, was recorded.

Synergy of 5-aminolevulinate supplement and CX3CR1 suppression promotes liver regeneration via elevated IGF-1 signaling.

Inadequate remnant volume and regenerative ability of the liver pose life-threatening risks to patients after partial liver transplantation (PLT) or partial hepatectomy (PHx), while few clinical treatments focus on safely accelerating regeneration. Recently, we discovered that supplementing 5-aminolevulinate (5-ALA) improves liver cold adaptation and functional recovery, leading us to uncover a correlation between 5-ALA metabolic activities and post-PLT recovery. In a mouse 2/3 PHx model, 5-ALA supplements enhanced liver regeneration, promoting infiltration and polarization of anti-inflammatory macrophages via P53 signaling.

Developing the modified 4-item version of perceived stress scale for functional dyspepsia.

Background: To develop the modified 4-item version of Perceived Stress Scale (PSS) with a better reliability and validity than the 4-item version of PSS (PSS-4) in evaluating psychological stress in patients with functional dyspepsia (FD). The present study also aimed to explore the correlation between dyspepsia symptoms severity (DSS), anxiety, depression, somatization, quality of life (QoL), and psychological stress assessed by two approaches in FD.

Methods: A total of 389 FD patients who met the Roman IV criteria completed the 10-item version of the PSS (PSS-10), and 4/10 items were selected by five methods, such as Cronbach's coefficient, exploratory factor analysis (EFA), correlation coefficient, discrete degree, and item analysis, to develop the modified PSS-4.

Developing the Patient Health Questionnaire-8 for a greater impact on the quality of life of patients with functional dyspepsia compared to Somatic Symptom Scale-8.

Background: To develop the Patient Health Questionnaire-8 (PHQ-8) as a more reliable approach than the Somatic Symptom Scale-8 (SSS-8), evaluating somatization which might be a critical factor influencing the quality of life (QoL) in patients with functional dyspepsia (FD). Also, the effects of somatization on QoL of FD patients were assessed by these two approaches.

Methods: Herein, 612 FD patients completed a questionnaire involving 25 items.

Association of Antenatal Micronutrient Supplementation With Adolescent Intellectual Development in Rural Western China: 14-Year Follow-up From a Randomized Clinical Trial.

Importance: The association of micronutrient supplementation during pregnancy with the intellectual development of adolescent offspring is unknown.

Objective: To assess the long-term association of antenatal micronutrient supplementation with adolescent intellectual development.

Design, Setting, And Participants: This 14-year follow-up study of a randomized clinical trial of micronutrient supplementation in pregnancy was conducted in 2 counties in rural western China in 2118 adolescent offspring (aged 10 to 14 years) of mothers who were randomized to take a daily capsule of either folic acid, folic acid plus iron, or multiple micronutrients from August 1, 2002, through February 28, 2006.

Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.

Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from premalignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe isolation and characterization of HCC progenitor cells (HcPCs) from different mouse HCC models.

Preclinical evaluation of the toxicological effects of a novel constrained ethyl modified antisense compound targeting signal transducer and activator of transcription 3 in mice and cynomolgus monkeys.

ISIS 481464 is a constrained ethyl (cEt) modified phosphorothioate antisense oligonucleotide (ASO) targeting signal transducer and activator of transcription 3 (STAT3) studied in mice and monkey to support oncology clinical trials. Six-week toxicology studies were performed in mice and cynomolgus monkey (up to 70 and 30 mg/kg/week respectively). Reduction in STAT3 protein up to 90% of control was observed in monkey.

p38α inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species.

Most hepatocellular carcinomas (HCC) develop in the context of severe liver fibrosis and cirrhosis caused by chronic liver inflammation, which also results in accumulation of reactive oxygen species (ROS). In this study, we examined whether the stress-activated protein kinase p38α (Mapk14) controls ROS metabolism and development of fibrosis and cancer in mice given thioacetamide to induce chronic liver injury. Liver-specific p38α ablation was found to enhance ROS accumulation, which appears to be exerted through the reduced expression of antioxidant protein HSP25 (Hspb1), a mouse homolog of HSP27.

Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production.

Innate immunity controls pathogen replication and spread. Yet, certain pathogens, such as Hepatitis C Virus (HCV), escape immune elimination and establish persistent infections that promote chronic inflammation and related diseases. Whereas HCV regulatory proteins that attenuate antiviral responses are known, those that promote inflammation and liver injury remain to be identified.

NF-κB and STAT3 - key players in liver inflammation and cancer.

Hepatocellular carcinoma (HCC), the major form of primary liver cancer, is one of the most deadly human cancers. The pathogenesis of HCC is frequently linked with continuous hepatocyte death, inflammatory cell infiltration and compensatory liver regeneration. Understanding the molecular signaling pathways driving or mediating these processes during liver tumorigenesis is important for the identification of novel therapeutic targets for this dreadful disease.

Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation.

The NF-kappaB activating kinase IKKbeta suppresses early chemically induced liver tumorigenesis by inhibiting hepatocyte death and compensatory proliferation. To study IKKbeta's role in late tumor promotion and progression, we developed a transplant system that allows initiated mouse hepatocytes to form hepatocellular carcinomas (HCC) in host liver after a long latency. Deletion of IKKbeta long after initiation accelerated HCC development and enhanced proliferation of tumor initiating cells.

Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression.

Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. To study how obesity augments cancer risk and development, we focused on hepatocellular carcinoma (HCC), the common form of liver cancer whose occurrence and progression are the most strongly affected by obesity among all cancers. We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice.

Targeted deletion of hepatocyte Ikkbeta confers growth advantages.

Mice lacking hepatocyte IKKbeta (Ikkbeta(Delta hep)) are defective in TNFalpha-activation of hepatocellular transcription factor NF-kappaB, and highly susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure, Ikkbeta(Delta hep) mice develop more hepatocellular carcinoma (HCC) than control mice due partly to enhanced DEN-induced hepatocyte death. Here we show that Ikkbeta(Delta hep) hepatocytes display growth advantages over normal hepatocytes consisting of precocious PCNA and cyclin D1 expression during liver regeneration (shortened hepatocyte G(0)-->G(1) transitions), and enhanced recovery efficiency, cyclin D1 expression and cell proliferation after plating.

Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis.

Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. We examined whether hepatocyte p38 alpha, found to inhibit liver carcinogenesis, acts similarly to IKK beta in control of ROS metabolism and cell death. Hepatocyte-specific p38 alpha ablation enhanced ROS accumulation and liver damage, which were prevented upon administration of an antioxidant.

The microvascular thrombi of colonic tissue in ulcerative colitis.

Mucosal microvascular thrombi in rectal biopsies were observed in some ulcerative colitis (UC). Heparin may be effective in steroid resistant UC in some studies, however, the new results of meta-analysis demonstrated a non-significant effect of heparin in controlled clinical trials, differing markedly from observational studies. The objective of this study was to identify colonic microvascular thrombi in larger cases with UC, and analyse its possible risk factors: age, gender, histologic score, extent of lesions and operation or biopsy specimens, and assess the significance of microvascular thrombosis in patients with UC.

Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin.

The EP2 prostanoid receptor is one of the four subtypes of receptors for prostaglandin E2 (PGE2). We previously reported that deletion of EP2 led to resistance to chemically induced mouse skin carcinogenesis, whereas overexpression of EP2 resulted in enhanced tumor development. The purpose of this study was to investigate the underlying molecular mechanisms.

Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity.

Thiazolidinediones are a novel class of antidiabetic drugs that improve insulin sensitivity in type 2 diabetic patients. Recently, these compounds have also been shown to suppress tumor development in several animal models. The molecular basis for their antitumor action, however, is largely unknown.

Troglitazone induction of COX-2 expression is dependent on ERK activation in keratinocytes.

Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis of several tissues, including skin. We report here that troglitazone, a thiazolidinedione class of antidiabetic drug, induced COX-2 expression at both the protein and mRNA levels and increased production of prostaglandin E2 (PGE2) in cultured keratinocytes. Troglitazone-induced COX-2 expression in keratinocytes was likely peroxisome proliferator-activated receptor gamma (PPARgamma)-independent.

Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development.

The EP2 receptor for prostaglandin E2 (PGE2) is a membrane receptor that mediates at least part of the action of PGE2. It has been shown that EP2 plays a critical role in tumorigenesis in mouse mammary gland and colon. However, the possibility that the EP2 receptor is involved in the development of skin tumors was unknown.

The effect of PPARgamma ligands on UV- or chemically-induced carcinogenesis in mouse skin.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated transcription factor. There have been suggestions that PPARgamma ligands may have utility in preventing tumor development in rodent mammary glands and colon. The recent finding that mice lacking one allele of the PPARgamma gene were significantly more susceptible to 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis compared to wild-type mice highlights mouse skin as another potential organ in which PPARgamma ligands may be effective as chemopreventive agents.

Troglitazone inhibits cyclin D1 expression and cell cycling independently of PPARgamma in normal mouse skin keratinocytes.

Troglitazone is one of the thiazolidinedione (TZD) class of anti-diabetic drugs and a ligand for peroxisome proliferator-activated receptor gamma (PPARgamma). Troglitazone and other PPARgamma ligands have been shown to inhibit cell proliferation and induce cell cycle arrest in a variety of cancer cells, and have been considered as potential tumor preventive and tumor therapeutic agents. Little is known, however, about how normal or initiated cells respond to these agents during mouse skin carcinogenesis.

[The preventive and therapeutic effects of low molecular weight heparin on DSS-induced colitis in mice].

Objective: To evaluate the preventive and therapeutic effects of low molecular weight heparin (LMWH) on dextran sulphate sodium (DSS)-induced colitis in mice.

Methods: Twenty normal mice were randomized into two groups: 10 mice of the prevention group received DSS per os and LMWH by sub-cutaneous injection for 7 days; 10 mice as controls received DSS per os and sub-cutaneous normal saline for 7 days. Another 20 mice with DSS-induced colitis were randomized into two groups: the treatment group received sub-cutaneous injection of LMWH and the control group received subcutaneous injection of normal saline for 7 days.