Gastric Dysfunction Research Articles

A pattern-recognition-based clustering method for non-invasive diagnosis and classification of various gastric conditions.

Conventional endoscopic biopsy tests are not suitable for early detection of the acute onset and progression of peptic ulcer as well as various gastric complications. This also limits its suitability for widespread population-based screening and consequently, many people with complex gastric phenotypes remain undiagnosed. Here, we demonstrate a new non-invasive methodology for accurate diagnosis and classification of various gastric disorders exploiting a pattern-recognition-based cluster analysis of a breathomics dataset generated from a simple residual gas analyzer-mass spectrometry. The clustering approach recognizes unique breathograms and "breathprints" signatures that clearly reflect the specific gastric condition of an individual person. The method can selectively distinguish the breath of peptic ulcer and other gastric dysfunctions like dyspepsia, gastritis, and gastroesophageal reflux disease patients from the exhaled breath of healthy individuals with high diagnostic sensitivity and specificity. Moreover, the clustering method exhibited a reasonable power to selectively classify the early-stage and high-risk gastric conditions with/without ulceration, thus opening a new non-invasive analytical avenue for early detection, follow-up, and fast population-based robust screening strategy of gastric complications in the real-world clinical domain.

Feasibility of mixed herbal medicine for improving gastric function in an alcohol-induced gastritis model.

Excessive exercise causes various gastric dysfunction. Gastritis is common among athletes who perform high-intensity training. Gastritis is a digestive disease involving mucosal damage caused by inflammatory reactions and oxidative stress. In this study, the effects of a complex natural extract on gastric mucosal damage and the expression of inflammatory factors were evaluated in an animal model of alcohol-induced gastritis. A mixed herbal medicine (Ma-al-gan; MAG) was prepared with four natural products (Curcumae longae Rhizoma, Schisandrae chinensis Fructus, Artemisiae scopariae herba, and Gardeniae Fructus) identified by a systemic analysis using the Traditional Chinese Medicine Systems Pharmacology platform. The effects of MAG on alcohol-induced gastric damage were evaluated. MAG (10-100 μg/mL) significantly reduced the mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells. MAG (500 mg/kg/d) effectively prevented alcohol-induced gastric mucosal injury in vivo. MAG regulates inflammatory signals and oxidative stress and is a potential herbal medicine for gastric disorders.

Review article: Functional dyspepsia-a gastric disorder, aduodenal disorder or a combination of both?

Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach. The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms. We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD. The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms. Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.

Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition.

Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine-mediated gastric inflammation. Mice were implanted with 25 mg slow-release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ-free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole. Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine-mediated gastric pathology was significantly attenuated in germ-free mice, and reconstitution of morphine gastric microbiome in germ-free mice resulted gastric inflammation. In addition, morphine-mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine-induced gastric dysbiosis and preventing inflammation. This study attributes morphine-induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine-associated pathophysiology.

Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation

Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging. Klotho mice were treated with the stable IGF1 analog LONG R3 recombinant human (rh) IGF1 (150 μg/kg intraperitoneally twice daily for 3 weeks). Gastric ICC/ICC-SC and signaling pathways were studied by flow cytometry, Western blot, and immunohistochemistry. Gastric compliance was assessed in exvivo systems. Transformation-related protein 53 was induced with nutlin 3a and ERK1/2 signaling was activated by rhIGF-1 in the ICC-SC line. LONG R3 rhIGF1 treatment prevented reduced ERK1/2 phosphorylation and gastric ICC/ICC-SC decrease. LONG R3 rhIGF1 also mitigated the reduced food intake and impaired body weight gain. Improved gastric function by LONG R3 rhIGF1 was verified by invivo systems. In ICC-SC cultures, rhIGF1 mitigated nutlin 3a-induced reduced ERK1/2 phosphorylation and cell growth arrest. IGF1 can mitigate age-related ICC/ICC-SC loss by activating ERK1/2 signaling, leading to improved gastric compliance and increased food intake in klotho mice.

Pancreatitis and the Risk of Developing Gastric Neuromuscular Dysfunction.

Most gastroparesis and functional dyspepsia cases (collectively, gastric neuromuscular dysfunction [GND]) remain idiopathic. It is believed that some idiopathic cases of GND may be triggered by an inflammatory insult to the gastrointestinal tract. We theorized that the profound foregut inflammation induced by pancreatitis could result in increased risk of GND. This was a case-control study of all patients undergoing gastric emptying scintigraphy between October 2017 and 2020 in an urban medical center with presumed GND. These were age-, sex-, and comparative health-matched to control patients with newly diagnosed microscopic colitis. Adjusted odds ratios (aORs) were calculated using conditional logistic regression. Among the 650 patients with GND, 359 had gastroparesis, and 9.2% had a history of acute pancreatitis (vs 3.1% of controls). Patients with GND demonstrated increased odds of having a history of acute pancreatitis (aOR 2.27, 95% confidence interval [CI] 1.33-4.03, P = 0.004) and recurrent pancreatitis (aOR 2.08, 95% CI 1.67-3.48, P = 0.002). Median time to GND diagnosis after first acute pancreatitis episode was 1,544 days (477.5, 3,832). Patients with a history of pancreatitis-associated GND had increased mortality vs controls (aOR 3.41, 95% CI 0.96-5.48). In addition, patients with pancreatitis-associated GND had more hospitalizations vs GND alone (13.8 vs 3.7, P < 0.0001) during the study period. This is the first study demonstrating an independent association between pancreatitis and the risk of GND, which occurred ∼4.2 years after the first episode of acute pancreatitis. Pancreatitis should therefore be regarded as a possible risk factor for developing GND with important consequences for healthcare utilization.

Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia.

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in "Synopsis of Golden Chamber" (Han Dynasty in the 3rd century) and the Zhizhu pill in "Differentiation on Endogenous" in Jin Dynasty (1,115-1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD). Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD. Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5g/kg, 1.0g/kg, or 1.5g/kg respectively) by gavage for 7days, while domperidone (3mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored. Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats. Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.

Robust Regression and Optimal Transport Methods to Predict Gastrointestinal Disease Etiology From High Resolution EGG and Symptom Severity.

Gastric functional and motility disorders are highly prevalent, with gastroparesis (GP) and functional dyspepsia (FD), affecting 1.5-3% and 10% of the population, respectively. Multiple disease etiologies with overlapping symptoms, such as antral hypomotility, pylorospasm, autonomic dysfunction, and gastric myoelectric dysfunction underlie GP and FD. There is an unmet need to differentiate these etiologies non-invasively to tailor treatment strategies and predict treatment response. We performed cutaneous high-resolution electrogastrogram (HR-EGG) recordings on 32 human subjects (controls, GP, and FD) and computed gastric slow wave propagation patterns. We implemented robust regression and clustering methods to identify one group of patients with symptoms well explained by spatial slow wave features and another with symptom severity significantly exceeding predictions from spatial slow wave features. Five patients were re-assessed with validated symptom questionnaires after pyloric and prokinetic interventions. A group of seven patients was identified whose spatial slow wave features lie within the same range as control subjects but whose symptom severity significantly exceeded what is predicted from spatial slow wave features. We hypothesize that gastric myoelectric dysfunction is not a prominent disease etiology in this group. A highly accurate regression holds in the other group of patients (r=0.8). Of the patients with repeat questionnaires, patients with symptom severity exceeding the regression line reported symptom improvement, whereas patients with symptoms in close proximity to the regression line experienced no improvement. These findings suggest that patients with symptom severity significantly exceeding the robust regression line have symptoms that cannot be explained by gastric myoelectric dysfunction alone, and vice versa. This methodology may provide clinicians with an opportunity to screen patients to determine when existing interventions will be effective, and on the flipside, when slow wave restoration interventions, such as gastric neuromodulation, may be most effective in improving symptoms and quality of life.

The Impact and Clinical Implications of Gastric Surgery on the Gastric Conduction System

Chronic symptoms of gastric dysfunction are common following gastric surgery, but the mechanisms underlying these have remained poorly understood. Disturbances of foregut motility are suspected to play a central role, however knowledge of how these abnormalities manifest and relate to symptoms requires elucidation. Emerging data suggests that abnormalities of the gastric conduction system are a common consequence of gastric surgery and may contribute to dysmotility and post-operative symptoms. This review provides a primer on the gastric conduction system. The normal physiology of the gastric conduction system and factors that influence resilience to surgery are outlined, together with focused discussion on three surgical procedures that impact post-operative gastric dysfunction: resection of the gastric pacemaker, resection or bypass of the pylorus, and vagotomy. The mechanistic pathways that underpin the clinical effects of these procedures are discussed. Future horizons are also evaluated, including newly established body surface gastric mapping techniques that provide a non-invasive method to detect changes in the gastric conduction system and relate these to symptoms in postoperative patients, with the goal of developing targeted interventions for prevention and therapy.

Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

Proximal and distal intragastric meal distribution during gastric emptying scintigraphy: Relationships to symptoms of gastroparesis.

Total gastric retention (TGR) from gastric emptying scintigraphy (GES) is used for diagnosing gastroparesis (Gp), but correlates poorly with patients' symptoms. Regional intragastric meal distribution (RIMD) can also be assessed from GES. This study classified patients' meal distribution as proximal or distal to relate RIMD to symptoms of Gp. GES studies in patients (n=193) and control subjects (n = 21) were selected for RIMD analysis. Patients completed Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM) for symptom severity before GES. TGR was analyzed using % TGR, and RIMD used a proximal/distal gastric count ratio (PDCR). Results were classified as proximal or distal RIMD at 0, 1, 2, and 4h postprandially based on their PDCR being above or below the median value of the patients. Patients with delayed GE and immediate post-meal ingestion distal distribution had more severe early satiety and regurgitation. Distal distribution at 1h had more severe early satiety and loss of appetite compared to proximal distribution. Patients with delayed GE and proximal distribution at 4h had more severe nausea, retching, and vomiting compared to 4h distal distribution. Severely delayed 4h proximal distribution had more nausea than severely delayed 4h distal distribution. Increased early distal IMD in patients with delayed GE was associated with regurgitation and early satiety whereas increased late proximal IMD was associated with nausea, retching, and vomiting. Differentiating proximal from distal meal distribution patterns helps to relate symptoms to gastric dysfunction and may be helpful for directing therapy.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

Retrospective Analysis of 128 Patients of Acupuncture Consultation After Pancreatic Surgery

Abstract?Objective: To analyze and summarie the the current situation of acupuncture consultation of postoperative patients for pancreatic caner in Qilu hospital of Shandong University and provide reference for acupuncture treatment of postoperative complications after pancreatic surgery.effect of acupuncture in treating gastrointestinal dysfunction after pancreatic surgery.Methods: Consultation reasons, diagnosis, treatments, patient compliance and effect of 128 cases from October 9,2020 to October 9,2021 was statistical analyzed. Result? A total of 128 patients were involved, 116 of those were completely treated. Effective rate of acupuncture for early postoperative inflammatory bowel obstruction was 94.85 % ?for postoperative gastric emptying dysfunction was 81.25% ? for early postoperative inflammatory bowel obstruction with gastric emptying disorder was 66.67 %and clinical total effective rate was 91.38 %.Conclusion: Acupuncture can promote pancreatic gastrointestinal function rehabilitation and provide new methods for enhanced recovery after surgery concept.

Opioid Use in Murine Model Results in Severe Gastric Pathology that May Be Attenuated by Proton Pump Inhibition

Opioids are the gold standard for chronic and acute pain management; however, their consequence on gastric function is relatively understudied. Opioid users have a higher incidence of gastric dysfunction, worse quality of life, increased hospitalizations, and increased use of antiemetic and pain modulator medications. The current study shows that morphine treatment in the murine model results in greater disruption of gastric epithelial cell morphology, increased gastric cell apoptosis, elevated inflammatory cytokines, and matrix metallopeptidase-9 secretion. Morphine treatment also increases gastric acid secretion and causes delays in gastric emptying. Moreover, morphine treatment causes an increase in systemic IL-6 level, which plays an important role in morphine-induced delayed gastric emptying and gastric damage. IL-6 knockout mice show a significant level of reduction in morphine-induced gastric delaying, acid retention, and gastric damage. Thus, morphine-mediated gastric damage is a consequence of the accumulation of acid in the stomach due to increased gastric acid secretion and delayed gastric emptying. Treatment with a proton pump inhibitor resulted in a significant reduction in morphine-induced gastric inflammation, gastric delaying, and improved morphine tolerance. Hence, these studies attribute morphine-mediated induction in gastric acidity and inflammatory cytokines as drivers for morphine-associated gastric pathology and show the therapeutic use of proton pump inhibitors as an inexpensive approach for clinical management of morphine-associated pathophysiology and analgesic tolerance.

Effect of Whole-Course Continuous Nursing Intervention Combined with a Nursing Practice Teaching Method on Quality of Life of Children with Functional Dyspepsia and Parents' Satisfaction Based on Smart Health.

With the development of information technology, it has become a part of people's lives. WeChat is not only a popular chatting tool in daily life but can also be used in the medical field. Functional dyspepsia is a common pediatric disease, with complex pathogenic factors, which are usually attributed to abnormal gastric acid secretion and gastrointestinal dysfunction. In our research, we aim to investigate the effects of whole-course continuous nursing intervention combined with a nursing practice teaching method on the quality of life (QOL) of children with functional dyspepsia and parents' satisfaction. One hundred and twenty children with functional dyspepsia admitted to our hospital (February 2019–February 2020) were retrospectively analyzed and equally divided into the experimental group (EG) and the control group (CG) according to the order of admission. The CG received whole-course continuous nursing intervention, and the EG received whole-course continuous nursing intervention combined with the nursing practice teaching method. Children's psychological states and QOL and parents' satisfaction of both groups were compared. After discharge, compared with the CG, the negative emotion scores in the EG were remarkably lower (P < 0.001). After discharge, compared with the CG, the QOL scores (P < 0.001), the proportion of children with good and excellent QOL (P < 0.05), and parents' satisfaction (P < 0.001) in the EG were remarkably higher. For children with functional dyspepsia, whole-course continuous nursing intervention combined with the nursing practice teaching method can improve their negative emotions, QOL, and parents' satisfaction, which should be popularized in practice.

Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years.

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Role of Macrophages and Mast Cells as Key Players in the Maintenance of Gastrointestinal Smooth Muscle Homeostasis and Disease.

The gut contains the largest macrophage pool in the body, with populations of macrophages residing in the mucosa and muscularis propria of the gastrointestinal (GI) tract. Muscularis macrophages (MMs), which are located within the muscularis propria, interact with cells essential for GI function, such as interstitial cells of Cajal, enteric neurons, smooth muscle cells, enteric glia, and fibroblast-like cells, suggesting that these immune cells contribute to several aspects of GI function. This review focuses on the latest insights on the factors contributing to MM heterogeneity and the functional interaction of MMs with other cell types essential for GI function. This review integrates the latest findings on macrophages in other organs with increasing knowledge of MMs to better understand their role in a healthy and diseased gut. We describe the factors that contribute to (muscularis macrophage) MM heterogeneity, and the nature of MM interactions with cells regulating GI function. Finally, we also describe the increasing evidence suggesting a critical role of another immune cell type, the mast cell, in normal and diseased GI physiology.

Design of a non-invasive sensing system for diagnosing gastric disorders

Gastric disorders are widely spread among the population of any age. At the moment, the diagnosis is made by using invasive systems that cause several side effects. The present manuscript proposes an innovative non-invasive sensing system for diagnosing gastric dysfunctions. The Electro-GastroGraphy (EGG) technique is used to record myoelectrical signals of stomach activities. Although EGG technique is well known for a long time, several issues concerning the signal processing and the definition of suitable diagnostic criteria are still unresolved. So, EGG is to this day a trial practice. The authors want to overcome the current limitations of the technique and improve its relevance. To this purpose, a smart EGG sensing system has been designed to non-invasively diagnose gastric disorders. In detail, the system records the gastric slow waves by means of skin surface electrodes placed in the epigastric area. Cutaneous myoelectrical signals are so acquired from the body surface in proximity of stomach. Electro-gastrographic record is then processed. According to the diagnostic model designed from the authors, the system estimates specific diagnostic parameters in time and frequency domains. It uses Discrete Wavelet Transform to obtain power spectral density diagrams. The frequency and power of the EGG waveform and the dominant frequency components are so analyzed. The defined diagnostic parameters are put in comparison with the reference values of a normal EGG in order to estimate the presence of gastric pathologies by the analysis of arrhythmias (&lt;em&gt;tachygastria&lt;/em&gt;, &lt;em&gt;bradygastria&lt;/em&gt; and irregular rhythm). The paper aims to describe the design of the system and of the arrhythmias detection algorithm. Prototype development and experimental data will be presented in future works. Preliminary results show an interesting relevance of the suggested technique so that it can be considered as a promising non-invasive tool for diagnosing gastrointestinal motility disorders.

Spinal cord injury-mediated changes in electrophysiological properties of rat gastric nodose ganglion neurons

In preclinical rodent models, spinal cord injury (SCI) manifests as gastric vagal afferent dysfunction both acutely and chronically. However, the mechanism that underlies this dysfunction remains unknown. In the current study, we examined the effect of SCI on gastric nodose ganglia (NG) neuron excitability and on voltage-gated Na+ (NaV) channels expression and function in rats after an acute (i.e. 3-days) and chronic (i.e. 3-weeks) period. Rats randomly received either T3-SCI or sham control surgery 3-days or 3-weeks prior to experimentation as well as injections of 3% DiI solution into the stomach to identify gastric NG neurons. Single cell qRT-PCR was performed on acutely dissociated DiI-labeled NG neurons to measure NaV1.7, NaV1.8 and NaV1.9 expression levels. The results indicate that all 3 channel subtypes decreased. Current- and voltage-clamp whole-cell patch-clamp recordings were performed on acutely dissociated DiI-labeled NG neurons to measure active and passive properties of C- and A-fibers as well as the biophysical characteristics of NaV1.8 channels in gastric NG neurons. Acute and chronic SCI did not demonstrate deleterious effects on either passive properties of dissociated gastric NG neurons or biophysical properties of NaV1.8. These findings suggest that although NaV gene expression levels change following SCI, NaV1.8 function is not altered. The disruption throughout the entirety of the vagal afferent neuron has yet to be investigated.

Duodenal Mucosal Barrier in Functional Dyspepsia

In addition to gastric sensorimotor dysfunctions, functional dyspepsia (FD) is also variably associated with duodenal micro-inflammation and epithelial barrier dysfunction, the pathogenesis and clinical significance of which are unknown. Our hypothesis was that miRNAs and/or inflammation degrade epithelial barrier proteins, resulting in increased duodenal mucosal permeability in FD. We compared the duodenal mucosal gene expression and miRNAs, invivo permeability (lactulose-mannitol excretion between 0 and 60 and 60 and 120 minutes after saccharide ingestion), exvivo assessments (transmucosal resistance, fluorescein isothiocyanate [FITC]-dextran flux, and basal ion transport), and duodenal histology (light and electron microscopy) in 40 patients with FD and 24 controls. Compared with controls, the mRNA expression of several barrier proteins (zonula occludens-1, occludin, claudin-12, and E-cadherin) was modestly reduced (ie, a fold change of 0.8-0.85) in FD with increased expression of several miRNAs (eg, miR-142-3p and miR-144-3-p), which suppress these genes. The urinary lactulose excretion and the lactulose:mannitol ratio between 60 and 120 minutes were greater in FD than in controls (P < .05). The FITC-dextran flux, which reflects paracellular permeability, was inversely correlated (r= -0.32, P= .03) with transmucosal resistance and directly correlated (r= 0.4, P= .02) with lactulose:mannitol ratio. Other parameters (mucosal eosinophils, intraepithelial lymphocytes, and mast cells, transmucosal resistance, FITC-dextran flux, average intercellular distance, and proportion of dilated junctions) were not significantly different between groups. In FD, there is a modest reduction in the expression of several duodenal epithelial barrier proteins, which may be secondary to up-regulation of regulatory miRNAs, and increased small intestinal permeability measured invivo.