World Journal of Gastroenterology最新文献

Background: The prognosis of critically ill patients is closely linked to their gastrointestinal (GI) function. The acute GI injury (AGI) grading system, established in 2012, is extensively utilized to evaluate GI dysfunction and forecast outcomes in clinical settings. In 2021, the GI dysfunction score (GIDS) was developed, building on the AGI grading system, to enhance the accuracy of GI dysfunction severity assessment, improve prognostic predictions, reduce subjectivity, and increase reproducibility.

Aim: To compare the predictive capabilities of GIDS and the AGI grading system for 28-day mortality in critically ill patients.

Methods: A retrospective study was conducted at the general intensive care unit (ICU) of a regional university hospital. All data were collected during the first week of ICU admission. The primary outcome was 28-day mortality. Multivariable logistic regression analyzed whether GIDS and AGI grade were independent risk factors for 28-day mortality. The predictive abilities of GIDS and AGI grade were compared using the receiver operating characteristic curve, with DeLong's test assessing differences between the curves' areas.

Results: The incidence of AGI in the first week of ICU admission was 92.13%. There were 85 deaths (47.75%) within 28 days of ICU admission. There was no initial 24-hour difference in GIDS between the non-survival and survival groups. Both GIDS (OR 2.01, 95%CI: 1.25-3.24; P = 0.004) and AGI grade (OR 1.94, 95%CI: 1.12-3.38; P = 0.019) were independent predictors of 28-day mortality. No significant difference was found between the predictive accuracy of GIDS and AGI grade for 28-day mortality during the first week of ICU admission (Z = -0.26, P = 0.794).

Conclusion: GIDS within the first 24 hours was an unreliable predictor of 28-day mortality. The predictive accuracy for 28-day mortality from both systems during the first week was comparable.

The growing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is being driven by the obesity epidemic. The quest for solutions continues particularly with regard to early detection. This editorial comments on the utility of long-term high-normal alanine aminotransferase (ALT) in screening for MASLD. Chen et al found that new onset MASLD can be detected by repetitively high normal ALT. Implicit in this concept is the question of what should be the accepted upper limit of normal (ULN) for ALT. It was previously set at 40 IU/L based on studies that included people with subclinical liver disease but the new consensus is 30/19 U/L in healthy males/females. Thus, when Chen et al defines the ULN as 40 U/L, others may view it as excessively high. It is important to recognize the variables affecting ULN e.g. instrumentation, diurnal variations, exercise and ageing. These variables matter when the distinctions are subtle e.g. normal vs high-normal. In this regard, the utility of long-term high normal ALT as a disease marker could be enhanced by combining it with other biomarkers, imaging and MASLD genetics to create machine learning classifiers. All in all, Chen et al's work on long-term high normal ALT as a marker of new-onset MASLD deserves merit.

Background: With the increasing of the global aging population, healthy aging and prevention of age-related diseases have become increasingly important. The liver, a vital organ involved in metabolism, detoxification, digestion, and immunity, holds a pivotal role in the aging process of organisms. Although extensive research on liver aging has been carried out, no bibliometric analysis has been conducted to evaluate the scientific progress in this area.

Aim: To analyze basic knowledge, development trends, and current research frontiers in the field via bibliometric methods.

Methods: We conducted bibliometric analyses via a range of analytical tools including Python, the bibliometrix package in R, CiteSpace, and VOSviewer. We retrieved publication data on liver aging research from the Web of Science Core Collection Database. A scientific knowledge map was constructed to display the contributions from different authors, journals, countries, institutions, as well as patterns of co-occurrence keywords and co-cited references. Additionally, gene regulation pathways associated with liver aging were analyzed via the STRING database.

Results: We identified 4288 articles on liver aging, authored by 24034 contributors from 4092 institutions across 85 countries. Notably, the years 1991 and 2020 presented significant bursts in publication output. The United States led in terms of publications (n = 1008, 25.1%), citations (n = 55205), and international collaborations (multiple country publications = 214). Keywords such as "lipid metabolism", "fatty liver disease", "inflammation", "liver fibrosis" and "target" were prominent, highlighting the current research hotspots. Notably, the top 64 genes, each of which appeared in at least 8 articles, were involved in pathways essential for cell survival and aging, including the phosphatidylinositol 3-kinase/protein kinase B, Forkhead box O and p53 signaling pathways.

Conclusion: This study highlights key areas of liver aging and offers a comprehensive overview of research trends, as well as insights into potential value for collaborative pursuits and clinical implementations.

In this article, we comment on the article by Huang et al. The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer. Tumor-associated macrophages (TAMs), primarily of the M2 subtype, are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways, including the wingless/integrated (Wnt) pathway. Activation of the Wnt signaling pathway is pivotal in promoting M2 TAMs polarization, which in turn can exacerbate hepatocarcinoma cell proliferation and migration. This manuscript emphasizes the burgeoning significance of the Wnt signaling pathway and M2 TAMs polarization in the pathogenesis and progression of liver cancer, highlighting the potential therapeutic benefits of inhibiting the Wnt pathway. Lastly, we point out areas in Huang et al's study that require further research, providing guidance and new directions for similar studies.

This letter comments on the recently published manuscript by Huang et al in the World Journal of Gastroenterology, which focused on the immunomodulatory effect of Calculus bovis on hepatocellular carcinoma (HCC) tumor microenvironments (TME) by inhibiting M2-tumor-associated macrophage (M2-TAM) polarization via Wnt/β-catenin pathway modulation. Recent research highlights the crucial role of TAMs and their polarization towards the M2 phenotype in promoting HCC progression. Epigenetic regulation, particularly through microRNAs (miR), has emerged as a key factor in modulating immune responses and TAM polarization in the TME, influencing treatment responses and tumor progression. This editorial focuses on miR-206, which has been found to inhibit HCC cell proliferation and migration and promote apoptosis. Moreover, miR-206 enhances anti-tumor immune responses by promoting M1-polarization of Kupffer cells, facilitating CD8+ T cell recruitment and suppressing liver cancer stem cell expansion. However, challenges remain in understanding the precise mechanisms regulating miR-206 and its potential as a therapeutic agent. Targeting epigenetic mechanisms and improving strategies, whether through pharmacological or genetic approaches, offer promising avenues to sensitize tumor cells to chemotherapy. Understanding the intricate interactions between cancer and non-coding RNA regulation opens new avenues for developing targeted therapies, potentially improving HCC prognosis.

Background: Helicobacter pylori (H. pylori) persistently colonizes the human gastric mucosa in more than 50% of the global population, leading to various gastroduodenal diseases ranging from chronic gastritis to gastric carcinoma. Cytotoxin-associated gene A (CagA) protein, an important oncoprotein, has highly polymorphic Glu-Pro-Ile-Tyr-Ala segments at the carboxyl terminus, which play crucial roles in pathogenesis. Our previous study revealed a significant association between amino acid deletions at positions 893 and 894 and gastric cancer.

Aim: To investigate the impact of amino acid deletions at positions 893 and 894 on CagA function.

Methods: We selected a representative HZT strain from a gastric cancer patient with amino acid deletions at positions 893 and 894. The cagA gene was amplified and mutated into cagA-NT and cagA-NE (sequence characteristics of strains from nongastric cancer patients), cloned and inserted into pAdtrack-CMV, and then transfected into AGS cells. The expression of cagA and its mutants was examined using real-time polymerase chain reaction and Western blotting, cell elongation via cell counting, F-actin cytoskeleton visualization using fluorescence staining, and interleukin-8 (IL-8) secretion via enzyme-linked immunosorbent assay.

Results: The results revealed that pAdtrack/cagA induced a more pronounced hummingbird phenotype than pAdtrack/cagA-NT and pAdtrack/cagA-NE (40.88 ± 3.10 vs 32.50 ± 3.17, P < 0.001 and 40.88 ± 3.10 vs 32.17 ± 3.00, P < 0.001) at 12 hours after transfection. At 24 hours, pAdtrack/cagA-NE induced significantly fewer hummingbird phenotypes than pAdtrack/cagA and pAdtrack/cagA-NT (46.02 ± 2.12 vs 53.90 ± 2.10, P < 0.001 and 46.02 ± 2.12 vs 51.15 ± 3.74, P < 0.001). The total amount of F-actin caused by pAdtrack/cagA was significantly lower than that caused by pAdtrack/cagA-NT and pAdtrack/cagA-NE (27.54 ± 17.37 vs 41.51 ± 11.90, P < 0.001 and 27.54 ± 17.37 vs 41.39 ± 14.22, P < 0.001) at 12 hours after transfection. Additionally, pAdtrack/cagA induced higher IL-8 secretion than pAdtrack/cagA-NT and pAdtrack/cagA-NE at different times after transfection.

Conclusion: Amino acid deletions at positions 893 and 894 enhance CagA pathogenicity, which is crucial for revealing the pathogenic mechanism of CagA and identifying biomarkers of highly pathogenic H. pylori.

Pancreatitis is a common, life-threatening inflammatory disease of the exocrine pancreas. Its pathogenesis remains obscure, and no specific or effective treatment is available. Gallstones and alcohol excess are major etiologies of pancreatitis; in a small portion of patients the disease is hereditary. Pancreatitis is believed to be initiated by injured acinar cells (the main exocrine pancreas cell type), leading to parenchymal necrosis and local and systemic inflammation. The primary function of these cells is to produce, store, and secrete a variety of enzymes that break down all categories of nutrients. Most digestive enzymes, including all proteases, are secreted by acinar cells as inactive proforms (zymogens) and in physiological conditions are only activated when reaching the intestine. The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens. It was proposed that pancreatitis results from proteolytic autodigestion of the gland, mediated by premature/inappropriate trypsinogen activation within acinar cells. The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis, and in human disease. On the basis of these observations, it has been considered the central pathogenic mechanism of pancreatitis - a concept with a century-old history. This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis, particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis; analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its' damaging effects; discusses the gaps in our knowledge, potential therapeutic approaches, and directions for future research. We conclude that trypsin is not the culprit in the disease pathogenesis but, at most, a mediator of some pancreatitis responses. Therefore, the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes, such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract that necessitate timely diagnosis to prevent complications and improve patient outcomes. Despite advancements in medical knowledge and diagnostic techniques, significant diagnostic delays persist, particularly in CD. The study by Blüthner et al, published in the World Journal of Gastroenterology, elucidates the diagnostic delays experienced by German patients with IBD and identifies key risk factors contributing to these delays.

The albumin-bilirubin (ALBI) score is derived from albumin and bilirubin levels. Currently, the ALBI score is widely used in various clinical settings. A recent article in the World Journal of Gastroenterology summarized the application of the ALBI score in various non-malignant liver diseases. The ALBI score has a predictive power that is superior or non-inferior to established numerous measures. This may be related to its contiguity, sensitivity, and inclusion of albumin. While we recognize the good results of the ALBI score in a number of diseases, the ALBI score also has limitations. Variation studies for population characteristics and other factors should be performed to validate the performance of ALBI. Further modifications or optimization of ALBI scores should be taken into account.

Background: Oral contrast-enhanced ultrasound (OCEUS) is widely used in the noninvasive diagnosis and screening of gastric cancer (GC) in China.

Aim: To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer.

Methods: OCEUS was performed before the operation, and standard ultrasound images were retained. The depth of infiltration of GC (T-stage) was evaluated according to the American Joint Committee on Cancer 8^th edition of the tumor-node-metastasis staging criteria. Finally, with postoperative pathological staging as the gold standard reference, the sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic value of OCEUS T staging were evaluated.

Results: OCEUS achieved diagnostic accuracy rates of 76.6% (T1a), 69.6% (T1b), 62.7% (T2), 60.8% (T3), 88.0% (T4a), and 88.7% (T4b), with an average of 75.5%. Ultrasonic T staging sensitivity exceeded 62%, aside from T1b at 40.3%, while specificity was over 91%, except for T3 with 83.5%. The Youden index was above 60%, with T1b and T2 being exceptions. OCEUS T staging corresponded closely with pathology in T4b (kappa > 0.75) and moderately in T1a, T1b, T2, T3, and T4a (kappa 0.40-0.75), registering a concordance rate exceeding 84%.

Conclusion: OCEUS was effective, reliable, and accurate in diagnosing the preoperative T staging of GC. As a noninvasive diagnostic technique, OCEUS merits clinical popularization.