The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

Pancreatic cancer (PC) remains a formidable challenge in oncology due to its notoriously poor prognosis, often resulting from late-stage diagnosis. Early detection through effective screening methods is crucial not only to improving patient outcomes but also to enhancing their quality of life. This review focuses on the latest advancements in PC screening and early diagnostic strategies. Key areas include the integration of artificial intelligence in radiology, the search for novel biomarkers, and the development of predictive models. This review aimed to provide a comprehensive overview, serving as a stepping stone toward transforming early detection strategies for PC in the digital age.

Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to provide medium- and long-term enteral nutrition to patients. Although generally considered safe, PEG tube placement can be associated with various potential complications. We report a case of gastrocolocutaneous fistula formation in a patient who presented with severe abdominal pain, new-onset diarrhea, and feculent emesis nine days after PEG tube placement. Awareness of this rare complication can facilitate the recognition of colonic perforation during gastrostomy tube placement and enable early detection of the complication post-procedurally. Additionally, we discuss various techniques that may be employed to prevent this complication during PEG tube placement.

Among all tumors worldwide, digestive tract tumors have a higher incidence rate and a significant disease burden. Esophageal cancer, gastric cancer, liver cancer, and colorectal cancer are often diagnosed at an advanced stage, and the prognosis remains poor. Currently, tumor treatment resistance is a major global challenge, with many underlying mechanisms. Ferroptosis has been shown to reverse drug resistance. This article reviews the mechanisms and recent advancements in ferroptosis related to reversing treatment resistance in gastrointestinal tumors, aiming to provide theoretical insights and research directions for the diagnosis and treatment of digestive tract tumors.

Previous studies suggest that taurine supplementation may attenuate atherosclerosis by reducing lipid levels. However, energy drinks containing taurine have been shown to increase blood pressure, a key risk factor for atherosclerosis. Thus, the role of taurine in atherosclerosis remains controversial. This study aimed to investigate the effect of taurine on the development of atherosclerotic plaques.

Plasma taurine levels were measured in 105 patients with varying degrees of coronary heart disease and in 40 healthy individuals using 1,2-13C2-taurine-based ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Apolipoprotein E knockout (ApoE−/−) C57BL/6J mice, fed a high-fat diet and subjected to left carotid artery ligation with cannula insertion, received taurine or saline for four consecutive days. Healthy control mice were fed a normal chow diet and underwent a sham operation. Serum taurine levels, lipid indicators, and arterial histology in the individual mice were examined.

Plasma taurine levels were significantly higher in patients with acute myocardial infarction (4.04 ± 0.24 μg/mL) compared to healthy controls (3.52 ± 0.22 μg/mL). Taurine treatment significantly decreased plaque areas in the carotid artery, reduced Masson’s Trichrome staining, and lowered the ratio of anti-α-SMA to anti-CD68 staining in ApoE−/− mice. Additionally, taurine treatment increased the levels of matrix metalloproteinase 2 in the cultured vascular endothelial cells in vitro.

These findings suggest that taurine supplementation may reduce both the size and stability of atherosclerotic plaques. Therefore, dietary taurine supplements should be used with caution.

Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, liver failure, or even death. While most patients respond well to first-line treatments, a significant number experience poor responses or intolerance, requiring the use of second- or third-line therapies. Ongoing research into the pathogenesis of AIH is leading to the development of novel therapeutic approaches. This review summarized recent advancements in the treatment of AIH both domestically and internationally.

Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

Chronic liver disease (CLD) represents a significant global health burden, with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease, and hepatitis C virus infection—being major contributors. Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) gene as a protective factor against the development and progression of these conditions. In this review, we summarized the current evidence surrounding the HSD17B13 rs72613567 variant, aiming to elucidate its impact on CLD risk and outcomes, and to explore the potential mechanisms behind its hepatoprotective effects. The rs72613567:TA variant induces a splice donor site mutation, resulting in a truncated, non-functional HSD17B13 protein. Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with MASH, alcoholic liver disease, and hepatitis C virus infection. Moreover, the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients. Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC. Furthermore, inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH. However, the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated. Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.

Over the course of the COVID-19 pandemic and its aftermath, growing concerns have emerged about the mental health of children and youth. Disease, loss, and lockdowns presented young people with enormous stressors, and much research suggests elevated levels of pediatric depression, anxiety, suicidality, and obsessive-compulsive behavior. However, considerable debate remains about the nature and persistence of these symptoms. This narrative review, conducted approximately four years after the onset of the pandemic, summarizes the major findings from four years of research, including empirical studies, meta-analyses, and systematic reviews. Studies were sourced from scholarly databases using the keywords “COVID-19”, “children”, “adolescents”, and “mental health”. The existing literature on the prevalence of depression in youth indicated that worldwide rates varied from 2.2% to 11.8% of the population, with one study revealing that one in four young people reported depressive symptoms. More specifically, 44% of youth in the United States demonstrated depression, while in China, the prevalence rate ranged from 11% to 44% of young people. Reviewed data showed that 20% of youth globally endorsed symptoms of anxiety or stress reactions, with countries such as Denmark (44%), Canada (45%), and the United States (32%) reporting extremely high rates. In the implications section, recommendations for screening and intervention procedures are outlined.

The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent acid suppressants, such as potassium-competitive acid blockers (P-CABs) like Vonoprazan, may improve eradication rates. The aim of this study was to compare the effectiveness of H. pylori eradication regimens containing Vonoprazan with those containing proton pump inhibitors for H. pylori infection.

Two hundred and thirty-two patients were assigned to two groups. Group I (treatment-naïve) included: Arm 1 (intervention arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Vonoprazan 20 mg twice daily; and Arm 2 (comparator arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Esomeprazole 20 mg twice daily. Group II (treatment-experienced) included: Arm 3 (intervention arm) with 58 patients who received Levofloxacin 500 mg once daily, Vonoprazan 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily; and Arm 4 (comparator) with 58 patients who received Levofloxacin 500 mg once daily, Esomeprazole 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily. All patients received their treatment regimens for 14 days. H. pylori eradication was assessed four weeks after treatment.

The successful eradication rate was higher in Arm 1 (58.6%) compared to Arm 2 (50%), and higher in Arm 3 (50%) compared to Arm 4 (43.1%). H. pylori eradication regimens including P-CABs were well-tolerated with a low incidence of adverse events.

The results of P-CAB-based eradication regimens are comparable to those of proton pump inhibitor-based regimens.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage. This results in progressive liver disease secondary to AAT polymerization and accumulation, and chronic obstructive pulmonary disease (COPD) due to deficient levels of AAT within the lungs. Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.

A subcohort of AATD individuals with COPD (n = 33) and AATD individuals without COPD (n = 14) were evaluated in this study from our previously reported cross-sectional cohort. We used immunohistochemistry to assess the AATD liver phenotype, and RNA sequencing to explore liver transcriptomics. We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.

A total of 339 genes were differentially expressed. Canonical pathways related to fibrosis, extracellular matrix remodeling, collagen deposition, hepatocellular damage, and inflammation were significantly upregulated in the livers of AATD individuals with COPD. Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.

Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present. We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

Despite its crucial role in interventional therapies for liver malignancy, cone-beam computed tomography (CBCT) has not yet been fully integrated into clinical practice due to several complicating factors, including nonstandardized operations and limited recognition of CBCT among interventional radiologists. In response, the Chinese College of Interventionalists has released a consensus statement aimed at standardizing and promoting the application of CBCT in the interventional therapies for liver malignancy. This statement summarizes CBCT scanning techniques, and operational standards, and highlights its potential applications in clinical practice.

(p)ppGpp binds to RNA polymerase, causing stalling at damaged DNA sites and subsequent backtracking, which facilitates the recognition and removal of damaged DNA by repair proteins. Additionally, (p)ppGpp regulates DNA repair proteins involved in the Save Our Soul response and mutagenic strand break repair pathways, which are crucial for repairing damages induced by Ultraviolet light and other DNA-damaging agents, including antibiotics. Through these repair pathways, (p)ppGpp plays a vital role in mending strand breaks induced by ciprofloxacin, a fluoroquinolone antibiotic. (p)ppGpp mediates bacterial survival by inhibiting the transcription of mismatch repair proteins while simultaneously upregulating error-prone polymerases mediated by stress-induced sigma factors, thereby facilitating mutagenesis. The function of (p)ppGpp in fine-tuning DNA repair proteins to support bacterial survival against antibiotics via stress-induced mutagenesis is an emerging topic in the field of antibiotic resistance research. Currently, limited information is available on how (p)ppGpp interconnects the various DNA repair pathways that directly influence bacterial resistance to antibiotics. (p)ppGpp is also known to promote bacterial persistence against ofloxacin, another fluoroquinolone, by regulating proteins that induce membrane depolarization. The overlapping functions of (p)ppGpp as a master regulator in DNA repair during stress and bacterial persistence are yet to be fully elucidated. This review focuses on recent publications highlighting (p)ppGpp as a potential link connecting DNA repair pathways to bacterial survival strategies against fluoroquinolone antibiotics.

Obesity has become a global epidemic affecting diverse populations and leading to metabolic syndrome across different sexes and age groups. A significant aspect of obesity is the development of leptin resistance, primarily due to the inefficient transport of leptin across the blood-brain barrier and other mechanisms such as protein folding and dysregulation of leptin signaling in brain areas related to energy and adipose tissue metabolism. This hindrance in leptin delivery poses a challenge to using this adipokine as a potential therapy for obesity. Current research focuses on understanding the complex molecular pathways that link diet-induced obesity, characterized by increased levels of leptin, to the onset of metabolic syndrome. This syndrome encompasses various health issues, including type 2 diabetes mellitus, and involves intricate mechanisms primarily affecting pancreatic β-cells. This bioinformatics-assisted review describes key biological elements of known pathways, such as the forkhead box protein O1/leptin receptor and Janus kinase/signal transducer and activator of transcription 3, and discusses future directions that might contribute to understanding the relationship between obesity, leptin resistance, and metabolic complications (e.g., Rac1/cell division control protein 42 homolog), paving the way for future research on targeted therapeutic interventions.