Research progress of TCM regulation of Cajal interstitial cells in the treatment of functional Gastrointestinal diseases

Interstitial cells of Cajal are a different class of cells with unique ultrastructure,molecular phenotype and function,and their main function is to generate slow waves,thereby triggering gastrointestinal pacing and regulating gastrointestinal motility.They play an extremely important physiological role in coordinating the normal activities of the digestive system,and their number,shape and function abnormalities often have a certain impact on gastrointestinal motility.Functional gastrointestinal disease is a type of digestive system disease closely related to gastrointestinal motility.Relevant studies have shown that the pathogenesis of functional gastrointestinal disease is closely related to the abnormal number,morphology and function of Cajal interstitial cells.Regulating the shape and number of interstitial cells of Cajal,maintaining the normal operation of gastrointestinal electrophysiology,inhibiting excessive autophagy and activating related signaling pathways,etc.,can improve gastrointestinal motility,thereby treating functional gastrointestinal diseases.This article will discuss the treatment of functional gastrointestinal diseases from traditional Chinese medicine compound,traditional Chinese medicine monomer,and external treatment of traditional Chinese medicine by regulating Cajal interstitial cells.

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.

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.

Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Criteria for assessing the diagnostic significance of modern methods of imaging gastrointestinal diseases in practical gastroenterology

Imaging methods are frequently used to diagnose gastrointestinal diseases and play a crucial role in verifying clinical diagnoses among all diagnostic algorithms.However,these methods have limitations,challenges,benefits,and advantages.Addressing these limitations requires the application of objective criteria to assess the effectiveness of each diagnostic method.The diagnostic process is dynamic and requires a consistent algorithm,progressing from clinical subjective data,such as patient history(anamnesis),and objective findings to diagnostics ex juvantibus.Caution must be exercised when interpreting diagnostic results,and there is an urgent need for better diagnostic tests.In the absence of such tests,preliminary criteria and a diagnosis ex juvantibus must be relied upon.Diagnostic imaging methods are critical stages in the diagnostic workflow,with sensitivity,specificity,and accuracy serving as the primary criteria for evaluating clinical,laboratory,and instrumental symptoms.A comprehensive evaluation of all available diagnostic data guarantees an accurate diagnosis.The“gold standard”for diagnosis is typically established through either the results of a pathological autopsy or a lifetime diagnosis resulting from a thorough examination using all diagnostic methods.

Nattokinase as a functional food ingredient:therapeutic applications and mechanisms in age-related diseases

Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.

Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.

Bacterial flora concurrent with Helicobacter pylori in the stomach of patients with upper gastrointestinal diseases

AIM： To investigate the non-He/icobacterpy/ori （H. pylori） bacterial flora concurrent with H. pylori infection.METHODS： A total of 103 gastric biopsy specimens from H. pylori positive patients were selected for bacterial culture. All the non-H, pylori bacterial isolates were identified by matrix assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF MS）.RESULTS： A total of 201 non-H, pyiori bacterial isolates were cultivated from 67 （65.0%） of the 103 gastric samples, including 153 isolates identified successfully at species level and 48 at genus level by MALDI-TOF MS. The dominant species were Streptococcus, Neisseria, Rothla and Staphylococcus, which differed fromthe predominantly acid resistant species reported previously in healthy volunteers. The prevalence of non-H. pylori bacteria was higher in non-ulcer dyspepsia group than in gastric ulcer group （100% vs 42.9%, P 〈 0.001）. Six bacterial species with urease activity （Staphylococcus epidermidis, Staphylococcus warneri, Staphylococcus capitis, Staphylococcus aureus, Brevibacteriurn spp. and Klebsiella pneumoniae） were also isolated.CONCLUSION： There is a high prevalence of the non-H, pylori bacteria concurrent with H. pylori infection, and the non-H, pylori bacteria may also play important as-yet-undiscovered roles in the pathogenesis of stomach disorders.

Gut microbiota in gastrointestinal diseases during pregnancy

Gut microbiota(GM)is a micro-ecosystem composed of all microorganisms in the human intestine.The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host.Dysbiosis of the GM may cause various diseases.GM has been demonstrated to be associated with human health and disease,and changes during individual development and disease.Pregnancy is a complicated physiological process.Hormones,the immune system,metabolism,and GM undergo drastic changes during pregnancy.Gastrointestinal diseases during pregnancy,such as hepatitis,intrahepatic cholestasis of pregnancy,and pre-eclampsia,can affect both maternal and fetal health.The dysregulation of GM during pregnancy may lead to a variety of diseases,including gastrointestinal diseases.Herein,we review recent research articles on GM in pregnancy-related gastrointestinal diseases,discuss the interaction of the GM with the host under normal physiological conditions,gastrointestinal diseases,and pregnancy-specific disorders.As more attention is paid to reproductive health,the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.

Update on clinical and research application of fecal biomarkers for gastrointestinal diseases

Gastrointestinal(GI) diseases comprise a large spectrum of clinical conditions ranging from indigestion to inflammatory bowel diseases(IBDs) and carcinomas. Endoscopy is the usual method employed to diagnose these condition. Another noninvasive way to assess and diagnose GI conditions are fecal biomarkers. Fecal biomarkers provide information regarding a specific disease process and are perhaps more acceptable to clinicians and patients alike because of their non-invasivity compared to endoscopy. Aim of this review was to evaluate the current status of the fecal biomarkers in clinical and research for in GI diseases. Multiple types of fecal biomarkers are discussed in this review including; markers to assess IBD, which are released as a results of an inflammatory insults to intestinal epithelia such as antimicrobial peptides(lactoferrin) or inflammation related proteins(calprotectin). While markers related to function of digestion are primarily related to partially digested food or mucosal proteins such as abnormal amount of fecal fat α1-antitrypsin, elastase and secretary IgA. The upcoming fecal biomarker like M2 pyruvate kinase and neutrophil gelatinase associated lipocalin are discussed as well. Apart from above mention, the fecal biomarkers under exploration for possible clinical use in future are also discussed. These include cathelicidins, osteoprotegerin, β-glucuronidase, Eosinophil proteins, etc.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast agents.To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years.The quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory disorders.However,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases.In this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

Use of endolumenal functional lumen imaging probe in investigating paediatric gastrointestinal motility disorders

Investigating gastrointestinal(GI)motility disorders relies on diagnostic tools to assess muscular contractions,peristalsis propagation and the integrity and coordination of various sphincters.Manometries are the gold standard to study the GI motor function but it is increasingly acknowledged that manometries do not provide a complete picture in relation to sphincters competencies and muscle fibrosis.Endolumenal functional lumen imaging probe(EndoFLIP)an emerging technology,uses impedance planimetry to measure hollow organs cross sectional area,distensibility and compliance.It has been successfully used as a complementary tool in the assessment of the upper and lower oesophageal sphincters,oesophageal body,the pylorus and the anal canal.In this article,we aim to review the uses of EndoFLIP as a tool to investigate GI motility disorders with a special focus on paediatric practice.The majority of EndoFLIP studies were conducted in adult patients but the uptake of the technology in paediatrics is increasing.EndoFLIP can provide a useful complementary data to the existing GI motility investigation in both children and adults.

Hematopoietic stem cell transplantation for non-malignant gastrointestinal diseases

Both, autologous and allogeneic hematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of malignant and non-malignant diseases. The rationale behind this strategy is based on the concept of immunoablation using high-dose chemotherapy, with subsequent regeneration of naive T-lymphocytes derived from reinfused hematopoietic progenitor cells. In addition, the use of HSCT allows for the administration of high-dose chemotherapy (whether or not combined with immunomodulating agents such as antithymocyte globulin) resulting in a prompt remission in therapy-refractory patients. This review gives an update of the major areas of successful uses of HSCT in non-malignant gastrointestinal disorders. A Medline search has been conducted and all relevant published data were analyzed. HSCT has been proved successful in treating refractory Crohn’s disease (CD). Patients with refractory celiac disease type II and a high risk of developing enteropathy associated T-cell lymphoma have shown promising improvement. Data concerning HSCT and mesenchymal SCT in end-stage chronic liver diseases are encouraging. In refractory autoimmune gastrointestinal diseases high-dose chemotherapy followed by HSCT seems feasible and safe and might result in long-term improvement of disease activity. Mesenchymal SCT for a selected group of CD is promising and may represent a significant therapeutic alternative in treating fistulas in CD.

Exosomes:A new frontier under the spotlight for diagnosis and treatment of gastrointestinal diseases

Exosomes are small plasma membrane-bound multivesicular bodies ranging in size from 20-100 nm.Exosomes are degraded fragments of mRNA,microRNA,and enriched in proteins,lipids,and nucleic acid.They are produced in the endosomes of most eukaryotic cells and once secreted,exosomes are involved in cell to cell communication and remodeling of the matrix in the extracellular compartment.Exosome biogenesis plays a crucial role in cellular development,inflammation,immunity,hemostasis,carcinogenesis,and degeneration.Due to their unique biochemical and biophysical properties,exosomes serve a variety of functions including biomarkers of diagnostic and prognostic significance.Besides,there is an increasing level of evidence to expand our understanding of the exosomes as novel therapeutic agents.Inflammatory bowel disease(IBD)such as Crohn's disease and ulcerative colitis,hepatic fibrosis,and gastrointestinal malignancies such as colorectal cancer are the potential avenues where exosomes can be applied as cell therapy and immunotherapy and have shown promising results in several in-vitro and animal models.The purpose of this review article is to highlight the emerging role of exosomes as the diagnostic and therapeutic tool in various diseases involving the gastrointestinal tract like IBD,hepatocellular carcinoma,and colon cancer.A thorough literature search was performed on databases such as PubMed,Ovid Medline,and EMBASE to achieve the objectives of this review article.

Balancing the Intestinal Microbiota to Treat Lower Gastrointestinal Diseases

Bacterial colonization is established by direct contact with maternal microorganisms immediately after birth,and may be affected during lactation.Increasing evidence shows that changes in the quantity and quality of the intestinal microbiota can help change the mucosal activation of the immune system,leading to intestinal or extraintestinal diseases.Throughout childhood and adolescence,the balance between pathogenic microbiota and beneficial microbiota is essential for gastrointestinal health,including the protection of pathogens,inhibition of pathogens,nutrient processing(vitamin K synthesis),and blood vessels where the stimulation of production and the regulation ofhost fat storage.Probiotics can promote the deliberate regulation of the intestinal microbiota,which is beneficial to the health of the host.The regulatory effects of intestinal microbiota on the prevention and adjuvant treatment of certain gastrointestinal diseases are reviewed.

Prevention and Treatment of Gastrointestinal Diseases in College Students

Objective:This paper aims to discuss the prevention and treatment strategies of gastrointestinal diseases in college students.Methods:A sample of 60 college students suffering from gastrointestinal diseases,from August 2021 to August 2022,was used to discuss the symptoms,causes,prevention strategies,and treatment strategies of gastrointestinal diseases based on questionnaire survey.Results:The high-incidence types of gastrointestinal diseases in college students mainly included chronic gastritis,acute gastritis,duodenal ulcer,and dyspepsia,which were closely related to mental state,diet,and living habits.Conclusion:There are many causes of gastrointestinal diseases in college students.During the period of active symptomatic treatment,it is necessary to focus on the prevention of gastrointestinal diseases in colleges and universities,correct the unhealthy lifestyle of students,and reduce the risk of gastrointestinal diseases.

Contribution of ghrelin to functional gastrointestinal disorders' pathogenesis

Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.

Circadian rhythms in the pathogenesis of gastrointestinal diseases

The etiology of digestive pathologies such as irritable bowel syndrome(IBS), inflammatory bowel diseases(IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms(chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets.

Epidemiology of functional gastrointestinal disorders in infants and toddlers: A systematic review

AIM: To assess the functional gastrointestinal disorders(FGID) prevalence in infants and toddlers. METHODS: Pub Med, EMBASE, and Scopus were searched for original articles from inception to February 2016. The literature search was made in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA). For inclusion, each study had to report epidemiological data of FGID on children up to 4 years old and contain standardized outcome Rome Ⅱ or Ⅲ criteria. The overall quality of included epidemiological studies was evaluated in accordance to Loney's proposal for prevalence studies of health literature. Two reviewers assessed each study for inclusion and extracted data. Discrepancies were reconciled through discussion.RESULTS: It was identified a total of 101 articles through the databases and two through the manual search. A total of 28 articles fulfilled the eligibility criteria. After reading the full articles, 13 of them were included in the present review. Twelve studies were written in English and one in Chinese, and published between 2004 and 2015. Eight articles(61.5%) were performed in Europe, three(23.1%) in America and two(15.4%) in Asia. Sample size varied between 45 and 9660 subjects. Cross-sectional frequency was reported in majority of studies(k = 9) and four studies prospectively followed the subjects. 27.1% to 38% of participants have met any of Rome's criteria for gastrointestinal syndromes, of those 20.8% presented two or more FGID. Infant regurgitation and functional constipation were the most common FGID, ranging from less than 1% to 25.9% and less than 1% to 31%, respectively. Most included studies were of moderate to poor data quality with respect to absence of confidential interval for prevalence rate and inadequate sampling methods.CONCLUSION: The scarcity and heterogeneity of FGID data call for the necessity of well-designed epidemiological research in different levels of pediatric practice and refinement of diagnostic.

Acupuncture treatment in gastrointestinal diseases: A systematic review

The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.