Gastric Disorders Research Articles

Tanacetum parthenium and parthenolide increase defensive agents and promote antisecretory activity supporting their gastroprotective actions in rodents

Tanacetum parthenium is popularly used to treat gastric disorders. However, the gastroprotective activity has not yet been tested. This study evaluated the anti-ulcer gastric effects of hydroalcoholic extract from T. parthenium (HETp) and parthenolide (PTL), its bioactive compound. Our findings revealed a significant reduction in HETp (10, 30, or 100 mg/Kg) and PTL (5 and 50 mg/Kg) in ethanol and piroxicam-induced ulcers, and this evidence was corroborated histologically. In addition, we explored the acid antisecretory activity by the pylorus ligation. Moreover, in mice pre-treated with the inhibitors indomethacin, L-NAME, and yohimbine, the antiulcerogenic effects of HETp and PTL were abolished, suggesting the involvement of nitric oxide, adrenergic receptors and prostaglandins in gastroprotective effects. Additionally, HETp and PTL prevented the depletion of SOD and CAT and decreased the activity of MPO and the levels of GSH and LPO. The results suggest that gastroprotection of HETp and PTL involves different pharmacological pathways.

Oral health statuses of individuals diagnosed with gastroparesis: A Cross-Section study.

Gastroparesis (GP) is a debilitating gastric motility disorder associated with digestive dysfunction, reduced quality of life (QoL), and increased mortality rates. There is no known cure for GP and treatment options are limited. The oral cavity is responsible for initiating digestion, yet the impact of GP symptom frequency on oral health status and oral healthcare utilization is not well understood. A 21-item electronic survey was developed and disseminated to a private GP social media forum. Survey questions explored GP symptom frequency, oral health status, dental care utilization, and oral health education post GP diagnosis. Descriptive and inferential statistics analysed data. There were 434 study participants. An overwhelming 83% reported GP negatively influenced their oral health and oral function. Significance was observed between GP symptom frequency and oral health status (p = <0.0001). The majority (81%) reported receiving dental care post GP diagnosis, yet (63%) reported current untreated dental concerns. Interestingly, (74%) of participants reported that they have never been educated about oral health risks associated with GP by any healthcare professionals. GP negatively affects oral health. Study participants reported a need for extensive dental treatments and high levels of untreated dental concerns. Results strongly support that preventive oral healthcare and education must be provided for individuals with a GP diagnosis. As leading oral disease prevention specialists, dental hygienists must be aware of the effects of GP on the oral cavity to help provide person-centred evidence-based care, improve digestive processes, and increase QoL for GP sufferers.

Ghrelin Modulates Voltage-Gated Ca2+ Channels through Voltage-Dependent and Voltage-Independent Pathways in Rat Gastric Vagal Afferent Neurons.

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca2+ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca2+ currents were inhibited with a log (Ic50) = -2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca2+ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca2+ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca2+ current inhibition was mediated by the Gα i/o or Gα q/11 family of subunits. Treatment with both PTX (Ca2+ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin's effects on Ca2+ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα i/o and Gα q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca2+ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin's regulation of gastric vagal afferents. SIGNIFICANCE STATEMENT: This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca2+ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders.

7276 Hypothyroid Patients With Gastric Diseases In Treatment With Liquid L-T4: An Observational Study

Abstract Disclosure: P. Fallahi: None. F. Ragusa: None. A. Patrizio: None. V. Mazzi: None. C. Botrini: None. G. Elia: None. E. Balestri: None. E. Barozzi: None. L. Rugani: None. E. Palmisano: None. M. Cosenza: None. G. Varricchi: None. S. Ulisse: None. S. Benvenga: None. S. Ferrari: None. A. Antonelli: None. We have conducted an observational and retrospective study, by enrolling patients with hypothyroidism and gastric diseases in treatment with liquid L-T4 (L-LT4) or tablet L-T4 (T-LT4). The aim of the study was to compare the stability of TSH in these patients. Eighty-four patients were in treatment with L-LT4, and 120 patients with T-LT4; all of them assumed L-T4 30 minutes before breakfast. The patients were affected by different types of gastric disease: a) in T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) in L-LT4 group: 60 CG; 3 GTx; 21 GP (p&amp;gt;0.05). In the T-LT4 group 66% of the patients were chronically treated with PPI, against 51% in the L-LT4 group (p&amp;gt;0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the two groups (p&amp;gt;0.05). The mean L-T4 dosage in the T-LT4 group at the basal evaluation was 1.22+/-0.27 μg/kg/die, in the L-LT4 group was 1.36+/-0.22 μg/kg/die (p&amp;gt;0.05). At the basal evaluation the prevalence of patients with a TSH &amp;gt; 3.5 μIU/mL in the T-LT4 group was 36%, whereas in the L-LT4 group was of 46% (p&amp;lt;0.05). After adjustment of the dosage of the LT-4 therapy, the patients were re-evaluated with an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of patients with a TSH&amp;gt;3.5 μIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of patients with a TSH &amp;gt; 3.5 μIU/mL in the T-LT4 group was 26%, and of 13% in the L-LT4 group (p&amp;lt;0.05). At the third re-evaluation, the prevalence of patients with TSH&amp;gt;3.5 μIU/mL in the T-LT4 group was 19%, and of 9% in the L-LT4 group (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH &amp;gt; 3.5 μIU/mL in the T-LT4 group was 18%, and of 5% in the L-LT4 group (p&amp;lt;0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. These data highlight a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up, by using a liquid L-T4 formulation therapy with respect to a tablet L-T4. Presentation: 6/3/2024

A Comprehensive Review of Coptidis Rhizoma and Magnoliae Officinalis Cortex Drug Pair and Their Chemical Composition, Pharmacological Effects and Pharmacokinetics Analysis.

Herbal pairs are unique combinations of two relatively fixed herbs that are used in clinical practice. This is the most fundamental and straightforward form of multiple herbal treatment that aims to attain specific efficacy through unique methods. Coptidis Rhizoma ("Huanglian" in Chinese) and Magnoliae Officinalis Cortex ("Houpo" in Chinese) which are commonly used in combination and could also be used as important components of other prescriptions to treat damp-heat dysentery, splenic and stomach disorders, and qi stagnation in clinical practice. However, there is currently no summary on the compatibility of Huanglian and Houpo about traditional use, phytochemistry, and pharmacological activity. It was found the combination or separate extraction of the two drugs may affect the main active components, and new components may be produced after the combined extraction. At the same time, Huanglian and Houpo herb pair exhibited antiviral, anti-inflammatory, antibacterial and other pharmacological effects. At present, research mainly focuses on the indicator components of Huanglian and Houpo, such as berberine, magnolol, and magnolol. The models used for pharmacological validation are limited, mainly including ulcerative colitis, pneumonia, bacterial infections, etc. In order to verify the pharmacological activity of the combination of Huanglian and Houpo, it is necessary to try more in vitro and in vivo models. It's still need to study the compatibility mechanism of the Huanglian and Houpo drug pair, including but not limited to the interactions between different components and the impact of compatibility on efficacy, bioequivalence studies, and the impact of different dosage forms on pharmacokinetics in the future. It's believed that the systematic review provided comprehensive information for the study of Huanglian-Houpo drug pair, which will help highlight the importance of the Huanglian-Houpo herb pair and provide some clues for future research on this herb pair.

Exploring the Antibacterial Activity of Ipomoea staphylina Extracts Against H. pylori: A Pharmacognostic Investigation of Whole Plant and Matured Stem with Emphasis on Quercetin Isolation.

Ipomoea staphylina Rome & Schult, entrenched in ethnomedicinal practices, is recognised for its efficacy in treating stomach disorders. Traditionally used in Dharmapuri, Tamil Nadu for stomach ulcers, its matured stem bark latex is therapeutically relevant, especially for Helicobacter pylori (H. pylori) infections. This prompts scientific exploration into its antibacterial properties. The research validates the antibacterial efficacy of I. staphylina extracts against H. pylori, scrutinising the whole plant and matured stem through a comparative pharmacognostic analysis. Utilising herbal standardisation techniques, we confirm the heightened purity of the powder. Antimicrobial assessments show exceptional efficacy of DME (dried Ethanolic extract of I. staphylina) and HLS (hydro alcoholic extract of I. staphylina) extracts. Quercetin isolation by using advanced instrumentation (Nuclear magnetic resonance [NMR], High resolution mass spectrometry [HR-MS], High-performance thin-layer chromatography [HPTLC], Fourier transform infrared spectroscopy [FTIR]) ensures precise compound identification. This methodology guarantees an exhaustive analysis, confirming purity and identifying bioactive components. Standardisation underscores the elevated purity of I. staphylina, with phytochemical screening revealing a predominant presence of phenolics and flavonoids. Antibacterial investigations highlight significant activity, particularly with DME and HLS extracts. These findings substantiate I. staphylina's medicinal significance, especially its matured stem latex, as a promising treatment for H. pylori-induced stomach ulcers, affirming traditional use by Dharmapuri villagers.

The Challenges of Treating a Helicobacter pylori Infection following the COVID-19 Pandemic in Croatia: A Review.

Background:Helicobacter pylori (H. pylori) is a prevalent bacterial pathogen implicated in different stomach and duodenal diseases, including chronic gastritis, gastric and duodenal ulcer, and stomach cancer. The COVID-19 pandemic has significantly influenced antibiotic prescription practices, potentially exacerbating antibiotic resistance in H. pylori. Objective: This study aims to investigate antibiotic prescription during the COVID-19 pandemic in Croatia and its possible impact on H. pylori antibiotic resistance, with a focus on Croatia. Methods: An extensive literature search was conducted to identify relevant studies from March 2020 to June 2024. The search strategy included terms related to COVID-19, antibiotic prescription, and Croatia. Studies were selected based on predefined eligibility criteria, focusing on observational research addressing antibiotic use during the pandemic. Results: The COVID-19 pandemic has led to significant fluctuations in community antibiotic consumption within the European Union/European Economic Area. In Croatia, antibiotic use in 2022 surpassed 2019 levels, driven by increased consumption of macrolides and other antibiotics. This surge, influenced by early pandemic treatment claims and penicillin shortages, contributed to rising antibiotic resistance in H. pylori. Resistance rates to clarithromycin and levofloxacin were notably high, driven by mutations in the 23S rRNA, gyrA, and gyrB genes. Discussion: The increased antibiotic use during the COVID-19 pandemic has highly likely complicated H. pylori eradication efforts, highlighting the necessity of judicious antibiotic use and robust antimicrobial stewardship. The pandemic underscored the need for new therapeutic strategies, optimized eradication regimens, and advanced diagnostic methods to manage bacterial infections effectively. Conclusions: The COVID-19 pandemic has significantly affected antibiotic use and resistance patterns, posing new challenges for H. pylori eradication. Addressing these challenges requires a multifaceted approach, including the development of new drugs and advanced diagnostics, coupled with sustained efforts in antimicrobial stewardship to combat emerging resistance threats.

Exploring the Experience of Guo Yi Master Lei Zhongyi in Dialectical Treatment of Heart Failure Based on the Theory of "Yang Wei Yin Xian"

The term "heart failure" first appeared in Wang Shuhe's "Meridian: Spleen and Stomach Diseases". The related description of heart failure is recorded in the "Huangdi Neijing", which is a disease mainly characterized by palpitations, asthma, and edema. It is often the terminal stage of chronic heart disease that cannot be cured. Its basic pathogenesis is prolonged illness with deficiency of heart qi, loss of nourishment in the heart, weakness in blood circulation, prolonged stagnation of the heart meridians, cessation of water consumption, and the generation of phlegm and dampness, resulting in heart failure. The theory of "Yang Wei Yin Xian" is a highly summarized understanding by Zhang Zhongjing of the etiology and pathogenesis of chest pain and heartache. Chinese medical master Lei Zhongyi has been practicing medicine for more than 60 years and has unique insights in the prevention and treatment of heart failure, with considerable clinical efficacy. He believes that heart failure belongs to the principle of deficiency and excess, and the theory of "yang micro yin string" is also applicable to this disease. Its onset is closely related to the pathological changes of substances such as qi, blood, and body fluids. The method of treating phlegm and blood stasis together should run through the treatment process, especially for patients who consume qi and yin in the later stage. Emphasis should be placed on promoting blood circulation and nourishing qi and yin, and the treatment should focus on both attacking and tonifying, with Qi and blood regulating simultaneously. Based on clinical experience, the original Yangxin Huoxue Tang has achieved significant clinical efficacy.

Discovery of Cinnamic Acid Derivatives as Potent Anti-H. pylori Agents

Antibiotics are currently used for the treatment of Helicobacter pylori (H. pylori), which is confirmed to be the major cause of gastric disorders. However, the long-term consumption of antibiotics has already caused antibiotic resistance and side effects in vivo. Therefore, there is an emerging need for searching for safe and effective anti-H. pylori agents. Inspired by the excellent bioactivities of cinnamic acid, a series of cinnamic acid derivatives (compounds 1–30) were synthesized and determined for H. pylori inhibition. The initial screening revealed that compound 23, a 2,4-dinitro cinnamic acid derivative containing 4-methoxyphenol, showed excellent H. pylori inhibition with an MIC value of 4 μM. Further studies indicated that compound 23 showed anti-bacterial activity and had a bactericidal effect on H. pylori due to the destruction of the bacterial structure. Molecular docking analysis revealed that the 2,4-dinitro groups in cinnamic acid moiety formed hydrogen bonding with amino acid residues in an active pocket of H. pylori protein. Interestingly, the ester moiety fitted into the hydrophobic pocket, attaining additional stability to compound 23. Above all, the present study reveals that compound 23 could be considered a promising anti-H. pylori agent to treat H. pylori causing gastritis.

Sinisan Alleviates Stress-Induced Intestinal Dysfunction and Depressive-like Behaviors in Mice with Irritable Bowel Syndrome by Enhancing the Intestinal Barrier and Modulating Central 5-Hydroxytryptamine

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice.

Design and Application of the New Multi-functional Moxibustion Box

Our team is dedicated to exploring new models for the treatment of spleen and stomach diseases using external therapy techniques of Traditional Chinese Medicine (TCM). We have developed a new multi-functional external therapy device for TCM that innovatively combines the concept of combined therapy with moxibustion. Additionally, through the application of artificial intelligence and new cross-industry intelligent manufacturing technologies, we have creatively incorporated an intelligent anti-burning system, enhancing the automation and informatization level of the product. We have implemented the concept of digitalization from the design stage, thus truly realizing an in-depth exploration of moxibustion, a method of external therapy in TCM. This chapter will summarize the design and application of a new multi-functional moxibustion box, aiming to provide a comprehensive reference for improving the symptoms of spleen and stomach diseases through moxibustion therapy.

GRB7-mediated enhancement of cell malignant characteristics induced by Helicobacter pylori infection.

Growth factor receptor bound protein 7 (GRB7) is reportedly upregulated in human gastric cancer (GC), which is closely associated with tumor progression and prognosis. However, the mechanism underlying its dysregulation in GC remains poorly understood. In this study, we found that GRB7 overexpression was associated with Helicobacter pylori (H. pylori) infection. GC cells (AGS and MGC-803) infection assays revealed that this upregulation was mediated by the transcription factor STAT3, and activation of STAT3 by H. pylori promoted GRB7 expression in infected GC cells. Moreover, CagA, the key virulence factor of H. pylori, was found involved in STAT3-mediated GRB7 overexpression. The overexpressed GRB7 further promoted GC cell proliferation, migration, and invasion by activating ERK signaling. Mice infection was further used to investigate the action of GRB7. In H. pylori infection, GRB7 expression in mice gastric mucosa was elevated, and higher STAT3 and ERK activation were also detected. These results revealed GRB7-mediated pathogenesis in H. pylori infection, in which H. pylori activates STAT3, leading to increased GRB7 expression, then promotes activation of the ERK signal, and finally enhances malignant properties of infected cells. Our findings elucidate the role of GRB7 in H. pylori-induced gastric disorders, offering new prospects for the treatment and prevention of H. pylori-associated gastric carcinogenesis by targeting GRB7.

Study on the clinical efficacy of 14-day vonoprazan-based triple regimen in obese patients with Helicobacter pylori infection

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

Advanced CNN models in gastric cancer diagnosis: enhancing endoscopic image analysis with deep transfer learning.

The rapid advancement of science and technology has significantly expanded the capabilities of artificial intelligence, enhancing diagnostic accuracy for gastric cancer. This research aims to utilize endoscopic images to identify various gastric disorders using an advanced Convolutional Neural Network (CNN) model. The Kvasir dataset, comprising images of normal Z-line, normal pylorus, ulcerative colitis, stool, and polyps, was used. Images were pre-processed and graphically analyzed to understand pixel intensity patterns, followed by feature extraction using adaptive thresholding and contour analysis for morphological values. Five deep transfer learning models-NASNetMobile, EfficientNetB5, EfficientNetB6, InceptionV3, DenseNet169-and a hybrid model combining EfficientNetB6 and DenseNet169 were evaluated using various performance metrics. For the complete images of gastric cancer, EfficientNetB6 computed the top performance with 99.88% accuracy on a loss of 0.049. Additionally, InceptionV3 achieved the highest testing accuracy of 97.94% for detecting normal pylorus, while EfficientNetB6 excelled in detecting ulcerative colitis and normal Z-line with accuracies of 98.8% and 97.85%, respectively. EfficientNetB5 performed best for polyps and stool with accuracies of 98.40% and 96.86%, respectively.The study demonstrates that deep transfer learning techniques can effectively predict and classify different types of gastric cancer at early stages, aiding experts in diagnosis and detection.

Terpenoids and steroids from aerial parts of Achillea alpina L. as PTP1B inhibitors: Kinetic analysis and molecular docking studies

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1–8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC50 values ranging from 14.87 to 23.09 μM in comparison with positive control - ursolic acid, showing IC50 value of 5.93 ± 0.16 μM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action.

Chemometric-based analysis and bioassay guided identification of potent compounds with intestinal motility promoting effects from Dalitong Granules

Ethnopharmacological relevanceDalitong Granules (DLT), a potent Traditional Chinese Medicine known for its ability to promote gastrointestinal motility, is widely used in clinical practice for the treatment of Functional Dyspepsia (FD). Despite the remarkable clinical efficacy of DLT, the specific components responsible for its effectiveness remains unclear. Aim of the studyThe study aimed to identify potential active ingredients of DLT for treating FD through spectrum-effect relationship analysis, multivariate statistical analysis and network pharmacology analysis. The efficacy of these identified compounds was subsequently validated using the zebrafish intestinal peristalsis model. Materials and methodsThe fingerprints of various solvent-extracted DLT were analyzed using high performance liquid chromatography coupled with tandem high-resolution mass spectrometry. The intestinal motility-promoting activities of DLT extracted by different solvents were evaluated through an intestinal propulsion test in mice. Potential therapeutic substances in DLT for treating FD were screened via chemometric analysis based on spectrum-effect relationship analysis. The correlation between the intensity of common peaks in the total ion chromatogram and the pharmacodynamic indices was assessed using multivariate statistical analysis. Additionally, given the complexity of Traditional Chinese Medicine, which comprises multiple components and targets, a network pharmacology analysis was performed to investigate the potential active ingredients in DLT. Finally, the pharmacological effects of these compounds in DLT were validated using a zebrafish intestinal motility model. ResultsThrough spectral-effect relationships analysis and network pharmacology analysis, it was determined that ten ingredients in DLT contribute to the promotion of intestinal motility. In a zebrafish intestinal motility model, it was observed that eight chemicals (excluding tetrahydropalmatine) demonstrate favorable activity of promoting gastrointestinal motility. These findings suggest that these ingredients may serve as potential therapeutic agents for improving gastric motility disorders. ConclusionsThis study employed spectral-effect relationship and network pharmacology analysis to identify the active ingredients in DLT. The findings were then validated using a zebrafish intestinal peristalsis model. These results provide a scientific foundation for the clinical application of DLT as a key traditional herbal formula for managing FD.

497. ENDOFLIP AND BOTULIN TOXIN INJECTION: THERAPEUTIC MANAGEMENT IN ESOPHAGEAL AND GASTRIC MOTILITY DISORDERS

Abstract Introduction Esophageal motility disorders present diagnostic and therapeutic challenges, with dysphagia being a common symptom prompting evaluation. The Endolumenal Functional Lumen Imaging Probe (EndoFLIP) has recently gained recognition as a valuable tool for assessing esophageal function. This study aims to evaluate the utility of EndoFLIP in guiding therapeutic interventions, specifically focusing on botulinum toxin injections, among patients presenting with diverse esophageal disorders. Moreover, the study acknowledges the potential of EndoFLIP as a diagnostic adjunct during diagnostic upper gastrointestinal endoscopy in cases where therapeutic alternatives are limited or as therapeutic trial. Methods A retrospective analysis was conducted on 21 patients who underwent EndoFLIP assessment and subsequently received botulinum toxin injection at the same procedure. These patients were identified from records at a tertiary center, covering the period from January 2022 to February 2023. EndoFLIP procedures were analyzed, focusing on patient symptoms and indication for the procedure. Data regarding clinical symptoms, EndoFLIP findings, and therapeutic interventions were extracted and analyzed to assess the role of EndoFLIP in guiding treatment decisions for esophageal disorders. The used cutoffs for esophagogastric junction (EGJ) distensibility index were &amp;lt; 2 mm2/mmHg and &amp;lt; 10 mm2/mmHg for pyloric distensibility. Results All patients referred for esophageal motility evaluation with EndoFLIP presented with dysphagia as the primary symptom. Two patients presented with postprandial bloating, leading to further evaluation with impedance planimetry to assess pyloric distensibility, suspected to be due to diabetic gastroparesis. Following EndoFLIP assessment, a conclusive diagnosis was achieved in all patients: 10 patients were diagnosed with esophagogastric junction outflow obstruction, 1 patient with absent contractility, 7 patients with achalasia, and 1 patient with hypercontractile esophagus. Patients who underwent planimetry to evaluate pyloric distensibility both exhibited reduced distensibility index. Following treatment, 10 patients showed clinical improvement and 11 await clinical reassessment. Conclusions Regarding the evaluation of the EGJ distensibility index in patients with achalasia without indication for invasive treatment, the EndoFLIP emerges as a diagnostic tool that allows for immediate guidance if intervention is recommended. Likewise, patients with refractory gastroparesis and pylorospasm identified through EndoFLIP may benefit from toxin injection for future myotomy decision. In conclusion, EndoFLIP serves as a valuable tool in diagnosing and guiding therapeutic interventions in patients with esophageal and gastric motility disorders. Further research is warranted to validate the role of EndoFLIP in optimizing treatment outcomes for esophageal disorders.

The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience.

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.

A novel compartmental approach for modeling stomach motility and gastric emptying

The stomach, a central organ in the Gastrointestinal (GI) tract, regulates the processing of ingested food through gastric motility and emptying. Understanding the stomach function is crucial for treating gastric disorders. Experimental studies in this field often face difficulties due to limitations and invasiveness of available techniques and ethical concerns. To counter this, researchers resort to computational and numerical methods. However, existing computational studies often isolate one aspect of the stomach function while neglecting the rest and employ computationally expensive methods. This paper proposes a novel cost-efficient multi-compartmental model, offering a comprehensive insight into gastric function at an organ level, thus presenting a promising alternative.The proposed approach divides the spatial geometry of the stomach into four compartments: Proximal/Middle/Terminal antrum and Pyloric sphincter. Each compartment is characterized by a set of ordinary differential equations (ODEs) with respect to time to characterize the stomach function. Electrophysiology is represented by simplified equations reflecting the “slow wave behavior” of Interstitial Cells of Cajal (ICC) and Smooth Muscle Cells (SMC) in the stomach wall. An electro-mechanical coupling model translates SMC “slow waves” into smooth muscle contractions. Muscle contractions induce peristalsis, affecting gastric fluid flow velocity and subsequent emptying when the pyloric sphincter is open. Contraction of the pyloric sphincter initiates a retrograde flow jet at the terminal antrum, modeled by a circular liquid jet flow equation.The results from the proposed model for a healthy human stomach were compared with experimental and computational studies on electrophysiology, muscle tissue mechanics, and fluid behavior during gastric emptying. These findings revealed that each “ICC” slow wave corresponded to a muscle contraction due to electro-mechanical coupling behavior. The rate of gastric emptying and mixing efficiency decreased with increasing viscosity of gastric liquid but remained relatively unchanged with gastric liquid density variations. Utilizing different ODE solvers in MATLAB, the model was solved, with ode15s demonstrating the fastest computation time, simulating 180 s of real-time stomach response in just 2.7 s. This multi-compartmental model signifies a promising advancement in understanding gastric function, providing a cost-effective and comprehensive approach to study complex interactions within the stomach and test innovative therapies like neuromodulation for treating gastric disorders.

Simultaneous Optical Imaging of Gastric Slow Waves and Contractions in the In Vivo Porcine Stomach.

Gastric peristalsis is governed by electrical "slow waves" generally assumed to travel from proximal to distal stomach (antegrade propagation) in symmetric rings. While alternative slow wave patterns have been correlated with gastric disorders, their mechanisms and how they alter contractions remain understudied. Optical electromechanical mapping, a developing field in cardiac electrophysiology, images electrical and mechanical physiology simultaneously. Here, we translate this technology to the in-vivo porcine stomach. Stomachs were surgically exposed and a fluorescent dye (di-4-ANEQ(F)PTEA) that transduces the membrane potential (Vm) was injected through the right gastroepiploic artery. Fluorescence was excited by LEDs and imaged with one or two 256x256 pixel cameras. Motion artifact was corrected using a marker-based motion tracking method and excitation ratiometry, which cancels common-mode artifact. Tracking marker displacement also enabled gastric deformation to be measured. We validated detection of electrical activation and Vm morphology against alternative non-optical technologies. Non-antegrade slow waves and propagation direction differences between the anterior and posterior stomach were commonly present in our data. However, sham experiments suggest they were a feature of the animal preparation and not an artifact of optical mapping. In experiments to demonstrate the method's capabilities, we found that repolarization did not always follow at a fixed time behind activation "wavefronts," which could be a factor in dysrhythmia. Contraction strength and the latency between electrical activation and contraction differed between antegrade and non-antegrade propagation. In conclusion, optical electromechanical mapping, which simultaneously images electrical and mechanical activity, enables novel questions regarding normal and abnormal gastric physiology to be explored.