Advancements in hemostatic strategies for managing upper gastrointestinal bleeding: A comprehensive review

Upper gastrointestinal(GI)hemorrhage presents a substantial clinical challenge.Initial management typically involves resuscitation and endoscopy within 24 h,although the benefit of very early endoscopy(<12 h)for high-risk patients is debated.Treatment goals include stopping acute bleeding,preventing rebleeding,and using a multimodal approach encompassing endoscopic,pharmacological,angiographic,and surgical methods.Pharmacological agents such as vasopressin,prostaglandins,and proton pump inhibitors are effective,but the increase in antithrombotic use has increased GI bleeding morbidity.Endoscopic hemostasis,particularly for nonvariceal bleeding,employs techniques such as electrocoagu-lation and heater probes,with concerns over tissue injury from monopolar electrocoagulation.Novel methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have limitations.Currently,the first-line therapy includes thermal probes and hemoclips,with over-the-scope clips emerging for larger ulcer bleeding.The gold probe,combining bipolar electrocoagulation and injection,offers targeted coagulation but has faced device-related issues.Future advancements involve combining techniques and improving endoscopic imaging,with studies exploring combined approaches showing promise.Ongoing research is crucial for developing standardized and effective hemorrhage management strategies.

A systematic scoping review of study methodology for randomized controlled trials investigating probiotics in athletic and physically active populations

Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of research on the effects of prob iotic supplementation in healthy athletes and physically active individuals.Considerable heterogeneity in probiotic selection and dosage as well as outcome measures has made clinical and mechanistic interpretation challenging for both health care practitioners and researchers.Attention to issues of randomization of participants,treatments and interventions,selection of outcomes,demographics,and reporting of adverse events will facilitate more trustworthy interpretation of probiotic study results and inform evidence-based guidelines.

Utilization of pH-driven methods to fortify nanoemulsions with multiple polyphenols

Simple but effective methods are required to incorporate multiple bioactive polyphenols into delivery systems to increase their dispersibility,stability and bioavailability.We developed and tested three p Hdriven protocols for creating nanoemulsions loaded with multiple lipophilic polyphenols.These protocols differed in how the different polyphenols were incorporated into the nanoemulsions.The impact of these three methods on the formation,properties,and gastrointestinal fate of nanoemulsions loaded with curcumin,resveratrol,and quercetin was investigated.The three methods produced nanoemulsions with similar initial particle properties:droplet diameters(0.15,0.16,and 0.15μm)and zeta-potentials(–59,–58,and–58 m V),respectively.However,the average encapsulation efficiencies(82%,88%,and 61%),gastrointestinal stabilities(83%,97%,and 29%)and bioaccessibilities(77%,90%,and 73%)for curcumin,resveratrol,and quercetin were somewhat different.In particular,more quercetin degradation occurred using the approach that held it under alkaline conditions for extended periods.In general,the p H-driven method provides researchers with a versatile approach of incorporating multiple polyphenols with different characteristics into functional food and beverages using a simple and inexpensive method.

Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI cancers.

Effect of simulated gastrointestinal digestion on antioxidant,and anti-inflammatory activities of bioactive peptides generated in sausages fermented with Staphylococcus simulans QB7

Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts from sausages fermented with Staphylococcus simulans QB7 during in vitro simulated GI digestion,including peptide profiles and antioxidant and anti-inflammatory activities.Peptides present in sausages were degraded during digestion,with molecular weight reduced from>12 kDa to<1.5 kDa.Besides,the content of amino acids increased from 381.15 to 527.07 mg/g,especially tyrosine being found only after GI digestion.The anti-inflammatory activities were increased after GI digestion,however,the changes in antioxidant activities were the opposite.A total number of 255,252 and 386 peptide sequences were identified in undigested,peptic-digested and GI-digested samples,respectively.PeptideRanker,BIOPEP-UWM and admetSAR were used to further predict the functional properties and intestinal absorption of the identified peptide sequences from GI digestion.Finally,18 peptides were discovered to possess either antioxidant or anti-inflammatory capacities.

Enteric neuropathy in diabetes:Implications for gastrointestinal function

Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

Clinical issues and challenges in imaging of gastrointestinal diseases:A minireview and our experience

Imaging techniques play a crucial role in the modern era of medicine,particularly in gastroenterology.Nowadays,various non-invasive and invasive imaging modalities are being routinely employed to evaluate different gastrointestinal(GI)diseases.However,many instrumental as well as clinical issues are arising in the area of modern GI imaging.This minireview article aims to briefly overview the clinical issues and challenges encountered in imaging GI diseases while highlighting our experience in the field.We also summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GI tract and demonstrate our experience in the area.In conclusion,almost all imaging techniques used in imaging GI diseases can also raise many challenges that necessitate careful consideration and profound expertise in this field.

Cronkhite-Canada syndrome with esophagus involvement and sixyear follow-up:A case report

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare,noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities.CCS polyps are distributed through the whole digestive tract,and they are common in the stomach and colon but very uncommon in the esophagus.CASE SUMMARY Here,we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea,alopecia,and loss of his fingernails.Laboratory data indicated anemia,hypoalbuminemia,hypocalcemia,hypokalemia,and positive fecal occult blood.Endoscopy showed numerous polyps scattered throughout the digestive tract,including the esophagus.He was treated with nutritional support and glucocorticoids with remission of his symptoms.CONCLUSION Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms.Treatment should be individualized for each patient according to their therapy response.Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

From macroautophagy to mitophagy:Unveiling the hidden role of mitophagy in gastrointestinal disorders

In this editorial,we comment on an article titled“Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases”,which was published in a recent issue of the World Journal of Gastroenterology.We focused on the statement that“autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal cells”.With advancing research,autophagy,and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system,has garnered extensive study.However,the significance of mitophagy,a unique selective autophagy pathway with ubiquitin-dependent and independent variants,should not be overlooked.In recent decades,mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases,especially inflammatory bowel disease,gastric cancer,and colorectal cancer.The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms,as well as for the development of novel treatment strategies.Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring.This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

Interaction between diet and genetics in patients with inflammatory bowel disease

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World Journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of microRNAs.In this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only way.Furthermore,we provided dietary recommendations for patients with IBD.The Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of IBD.On the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)patients.According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD patients.For patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red meats.In conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes.Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)cells.However,the role of autophagy in GI diseases remains controversial.This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children

BACKGROUND The detection rate of peptic ulcer in children is improving,with development of diagnostic procedures.Gastroscopy is the gold standard for the diagnosis of peptic ulcer,but it is an invasive procedure.Gastrointestinal contrast-enhanced ultrasonography(CEUS)has the advantages of being painless,noninvasive,nonradioactive,easy to use,and safe.AIM To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children.METHODS We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022.All children were examined by routine ultrasound,gastrointestinal CEUS,and gastroscopy.The pathological results of gastroscopy were taken as the gold standard.Routine ultrasonography was performed before gastrointestinal CEUS.Conventional ultrasound showed the thickness of the gastroduodenal wall,gastric peristalsis,and the adjacent organs and tissues around the abdominal cavity.Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall;the size,location and shape of the ulcer;gastric peristalsis;and adjacent organs and tissues around the abdominal cavity.The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS.All children received informed consent from their guardians for CEUS.This study was reviewed and approved by the hospital medical ethics committee.RESULTS Among the 43 children,17(15 male,2 female)were diagnosed with peptic ulcer by gastroscopy.There were 26 children with nonpeptic ulcer.There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound.The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1%(34/43),which was significantly different from that of gastroscopy(P=0.033).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low.Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS.The diagnostic coincidence rate of peptic ulcer in children was 95.3%(41/43).There was no significant difference between CEUS and gastroscopy(P=0.655).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high.CONCLUSION Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children,and can be used as a preliminary examination method.

Outpatient management of obscure gastrointestinal bleeding:A new perspective in high-risk patients

Mid-gastrointestinal bleeding accounts for approximately 5%-10%of all gastrointestinal bleeding cases,and vascular lesions represent the most frequent cause.The rebleeding rate for these lesions is quite high(about 42%).We hereby recommend that scheduled outpatient management of these patients could reduce the risk of rebleeding episodes.

Stability and transepithelial transport of oligopeptide(KRQKYD)with hepatocyte-protective activity from Jinhua ham in human intestinal Caco-2 monolayer cells

The study evaluated the stability of an oligopeptide(Lys-Arg-Gln-Lys-Tyr-Asp,KRQKYD)and its transport mechanism by simulating gastrointestinal digestion and a model of human intestinal Caco-2 monolayer cells in vitro.In this study,the effects of environmental factors(temperature,pH and NaCl concentration)and simulated gastrointestinal digestion on the stability of KRQKYD were evaluated by indicators of the levels of alanine transaminase(ALT),aspartate transaminase(AST)and malondialdehyde(MDA)in an alcoholinduced hepatocyte injury model.The results showed that KRQKYD still maintained satisfactory hepatocyteprotective activity after treatment with different temperatures(20-80℃),pH(3.0-9.0),NaCl concentration(1%-7%)and simulated gastrointestinal digestion,which indicated that KRQKYD showed good stability to environmental factors and simulated gastrointestinal digestion.Furthermore,the intact KRQKYD could be absorbed in a model of Caco-2 monolayer cells with a P_(app)value of(9.70±0.53)×10^(-7)cm/s.Pretreatment with an energy inhibitor(sodium azide),a competitive peptide transporter inhibitor(Gly-Pro)and a transcytosis inhibitor wortmannin did not decrease the level of transepithelial KRQKYD transport,indicating that the transport mechanism of KRQKYD was not associated with energy dependent,vector mediated and endocytosis.The tight junction disruptor cytochalasin D significantly increased the level of transepithelial KRQKYD transport(P<0.05),suggesting that intact KRQKYD was absorbed by paracellular transport.

Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary tract.It should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather insufficient.The exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be available.The most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries.The existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from childhood.Changes that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of carcinogenesis.Even these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms.Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required.In this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis.Finally,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors

In this editorial,we review the article published in World J Gastrointest Oncol 2019,11:1031-1042.We specifically focus on the occurrence,clinical characteristics,and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors.Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors,the incidence and mortality rates of treatment-related car-diotoxicity have been increasing,severely impacting the survival and prognosis of cancer patients.Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors,including gastrointestinal tumors,and they represent the second largest class of drugs associated with cardiotoxicity.However,there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.

Interleukin-1β:Friend or foe for gastrointestinal cancers

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.