Portal hypertension can cause serious complications such as upper gastrointestinal bleeding, primarily due to esophageal and gastric varices. The risk of mortality from variceal hemorrhage is significant, particularly when the hepatic venous pressure gradient exceeds 12 mmHg. Established treatments generally include endoscopic variceal band ligation and cyanoacrylate glue for gastric varices; however, challenges such as limited availability and a lack of technical expertise can hinder the use of glue, leading to preventable complications. This study investigates the efficacy of using a 50% glucose solution for injection sclerotherapy in cases of gastric varices. We present three unique patient cases. The first case involves a 21-year-old with persistent upper gastrointestinal bleeding and a portal vein thrombus, who experienced temporary relief after receiving injection sclerotherapy but tragically succumbed to significant bleeding later. The second case describes a 24-year-old who successfully managed his bleeding with the same treatment but was subsequently lost to follow-up. Lastly, a 72-year-old patient with recurrent painless hematemesis remained free of symptoms following injection sclerotherapy. Overall, while cyanoacrylate glue remains the preferred treatment, injection sclerotherapy with 50% dextrose shows promise as an effective alternative, particularly in settings where conventional treatments are not readily available, potentially reducing the risks associated with untreated variceal bleeding.

Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact of different oxygen therapy modalities on oxidative stress by comparing malondialdehyde (MDA) levels, an oxidative stress marker, and glutathione (GSH), an antioxidant marker, in patients with severe COVID-19 pneumonia.

This study included 50 patients with COVID-19 pneumonia who received oxygen therapy using a reservoir mask at ≥15 L/m, high-flow oxygen therapy at 60 L/m, or oxygen therapy with noninvasive mechanical ventilation at fraction of inspired O2 (FiO2) levels of ≥60%. GSH and MDA levels were measured 48 h after starting oxygen therapy at FiO2 ≥ 60% and 48 h after switching to nasal cannula oxygen therapy at 2–4 L/m.

Overall, 60% (n = 30) of the patients were men, and 40% (n = 20) were women. In patients with accompanying hypertension, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.046). A significant difference in MDA was not found after switching to lower oxygen flow (p = 0.064) in patients with underlying diabetes mellitus. GSH levels in patients with underlying diabetes mellitus were higher during oxygen therapy at FiO2 ≥ 60% and decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.021).

This study compared MDA and GSH levels among patients receiving oxygen therapy at high and low concentrations for severe COVID-19 pneumonia. The results revealed that patients who died of COVID-19 pneumonia had significantly higher mean MDA levels than those who survived. In patients with underlying HT, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased during nasal oxygen therapy at 2–4 L/m; this difference was significant. The increase in serum MDA levels during high-flow oxygen therapy and the decrease during low-flow therapy in patients with COVID-19 pneumonia accompanied by hypertension suggest that oxidative stress due to hyperoxia should be taken into consideration.

Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years.

Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed.

In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40–75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China.

A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease characterized by autoimmune-mediated hepatic injury. Currently, glucocorticoid drugs, primarily prednisone, with or without azathioprine, are commonly recommended as first-line therapeutic agents in treatment guidelines by many scientific associations. However, the primary objective of treatment is to achieve a complete biochemical response, which is defined as the normalization of both transaminases and immunoglobulin G levels within six to twelve months. Ideally, this should also be accompanied by histological remission. Nevertheless, corticosteroid therapy is associated with significant adverse effects, potentially resulting in treatment discontinuation. In this context, it has become evident that standard treatment is inadequate for a proportion of patients, leading to the emergence of other treatment options and lines. Novel immunomodulatory agents, a class of drugs that regulate the body’s immune functions, have been confirmed to possess properties that modulate immune balance and induce immune tolerance. In recent years, these agents have played an increasingly significant role in the clinical management of AIH. This article provided an in-depth review of recent advancements in the development of novel immunomodulators, including immune cell nucleic acid inhibitors, calmodulin phosphate inhibitors, mammalian target of rapamycin inhibitors, tumor necrosis factor-α inhibitors, interleukin-2, anti-CD20 monoclonal antibodies, and B cell-activating factor inhibitors, for the treatment of AIH.

Waist circumference (WC) is closely associated with metabolic diseases, including diabetes mellitus (DM), metabolic syndrome, and mortality. However, the correlation between WC and mortality varies across populations and has rarely been examined specifically in patients with DM. In this study, we explored the relationships between WC and both all-cause and cardiovascular mortalities among individuals with DM.

Participants from the National Health and Nutrition Examination Survey 2003–2018 included 3,151 women and 3,473 men with DM who had baseline WC measurements. Survival data were collected from enrollment until December 31, 2019. Cox proportional hazard models were adjusted for demographic features and other confounders. Restricted cubic spline curves and threshold effect analyses were performed separately for men and women. Sensitivity analyses were conducted to minimize reverse causality.

Among 6,624 participants with DM, 621 women and 871 men died during median follow-ups of 6.8 and 6.3 years, respectively. WC demonstrated a U-shaped association with all-cause and cardiovascular mortalities in women, and a J-shaped trend in men. The optimal WC thresholds for minimizing mortality risk were 107.0 cm for women and 89.0 cm for men. For women, adjusted hazard ratios for all-cause mortality were 0.97 (95% confidence interval (CI): 0.96–0.98, P < 0.001) for WC below 107.0 cm and 1.04 (95% CI: 1.02–1.05, P < 0.001) for WC above 107.0 cm. In men, the corresponding ratios were 0.94 (95% CI: 0.90–0.97, P < 0.001) for WC below 89.0 cm and 1.03 (95% CI: 1.02–1.05, P < 0.001) for WC above 89.0 cm.

WC showed a U-shaped association with all-cause and cardiovascular mortalities in women and a J-shaped association in men among U.S. adults with DM from the National Health and Nutrition Examination Survey. Further research is needed to explore the underlying mechanisms rather than promoting preconceived notions about an optimal WC.

Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to efficiently deliver therapeutic cargo. These systems, primarily based on synthetic and natural polymers, offer significant advantages in terms of safety, controlled gene release, and targeted delivery. This review explores the design and synthesis of macromolecular carriers, focusing on their chemical and physical architectures, which play a key role in improving gene delivery. Catanionic polymers and their derivatives (comb, brush, and star polymers) have been extensively researched for their capacity to condense and protect genetic material. Furthermore, natural polymers like chitosan and hyaluronic acid have been modified to enhance gene delivery capabilities. These macromolecular carriers are engineered to boost circulation time, increase cellular uptake, and facilitate the controlled release of genetic material at the target site. Strategies such as incorporating targeting ligands, stimuli-responsive elements, and reducing cytotoxicity are being pursued to improve the overall efficiency and specificity of these systems. This review highlights the current state of macromolecular gene delivery systems, their applications, and the ongoing research aimed at overcoming existing challenges, paving the way for more effective non-viral gene therapies.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

Protein disulfide isomerases (PDIs) are essential enzymes that facilitate the proper folding of proteins and maintain protein quality within the endoplasmic reticulum. Dysregulation of PDIs has been correlated with numerous disorders, including cancer and rheumatoid arthritis (RA). E64FC26 (EFC), a small molecule that inhibits a wide range of PDI family members, has shown promise as a therapeutic agent in oncology. However, its effects on RA have not yet been studied. This research investigates the efficacy of EFC as a potential treatment for RA.

To investigate EFC’s effects on RA fibroblast-like synoviocytes, several assays were employed, including Cell Counting Kit-8 for cell viability, EdU for cell proliferation, Transwell for migration and invasion, TUNEL for apoptosis, and in vitro tube formation assays for angiogenesis. Flow cytometry was used to assess apoptosis in detail. Cytokine production was analyzed using ELISA and real-time polymerase chain reaction. In vivo, a collagen-induced arthritis model was developed in DBA mice to evaluate EFC’s effects on inflammation, disease progression, and bone damage. RNA sequencing was utilized to identify the molecular pathways influenced by EFC treatment.

EFC exhibited significant anti-inflammatory effects on RA fibroblast-like synoviocytes, reducing cell proliferation, migration, invasion, angiogenic activity, and cytokine secretion, while simultaneously promoting apoptosis. In vivo experiments using the collagen-induced arthritis mouse model showed that EFC alleviated inflammation, slowed disease progression, and preserved joint and bone integrity. RNA sequencing data suggested that EFC acts through pathways associated with inflammation and apoptosis regulation.

The findings of this research underscore EFC’s therapeutic potential in managing RA. These results pave the way for the development of inhibitors targeting the PDI family as innovative treatments for RA.

Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.

Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.

Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1–0.4%), and only one patient was HDV RNA positive.

The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.