TRPV1 Dysfunction Impairs Gastric Nitrergic Neuromuscular Relaxation in High-Fat Diet-Induced Diabetic Gastroparesis Mice.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying of solid food. Nitrergic neuron-mediated fundus relaxation and intragastric peristalsis are pivotal for gastric emptying and are impaired in DGP. Transient receptor potential vanilloid 1 (TRPV1) ion channels are expressed in gastrointestinal vagal afferent nerves and have a potential role in relevant gastrointestinal disorders. In this study, mice with high-fat diet (HFD)-induced type 2 diabetes mellitus (T2DM), associated with gastroparesis, were used to determine the role of TRPV1 in DGP. After feeding with HFD, mice exhibited obesity, hyperglycemia, insulin resistance, and delayed gastric emptying. Cholinergic- and nitrergic neuron-mediated neuromuscular contractions and relaxation were impaired. The antral tone of the DGP mice was attenuated. Interestingly, activating or suppressing TRPV1 facilitated or inhibited gastric fundus relaxation in normal mice. These effects were neutralized by using a nitric oxide synthase (NOS) inhibitor. Activation or suppression of TRPV1 also increased or reduced NO release. TRPV1 was specifically localized with neuronal NOS in the gastric fundus. These data suggest that TRPV1 activation facilitates gastric fundus relaxation by regulating neuronal NOS and promoting NO release. However, these effects and mechanisms disappeared in mice with DGP induced by HFD diet. TRPV1 expression was only marginally decreased in the fundus of DGP mice. TRPV1 dysfunction may be a potential mechanism underlying the dysfunction of DGP gastric nitrergic neuromuscular relaxation.

Crohn's disease with multiple jejunum and ileum lesions: A case report.

Crohn's disease (CD) affecting the jejunum and ileum is uncommon and its diagnosis can be challenging. This case report describes a 35 year old male patient who had been e xper iencing intermi ttent periu mbilica l pain , di arrho ea and fever for five years. Despite undergoing gastroscopy, co lo noscopy and capsule endoscopy; no s ignific ant abnormal ities were found. This case was se en at the Shenzhen Ho spital of Traditional Chinese Medi ci ne; Shenzhen, China. However, the pa tient u nder went a doubl e-balloon enteroscopy (DBE), which revealed multip le ulcers in the jejunum and ileum, leadin g to a confirmed diagnosis of CD. The patient was successfully treated with infliximab t o rel ieve sy mptoms. DBE can be par ticularly valuable in diagnosing CD in young patients with symptoms when conventional endoscopic techniques have been unsuccessfu l. This case highlights the impor tance of considering small bowel disease in patients wit h CD symptoms and the potential benefits of DBE in diagnosing such cases.

Resection of an anal fistula with endoscopic submucosal dissection.

A 34-year-old man presented with paroxysmal hypogastralgia during defecation for 2 weeks. Physical and laboratory examination findings were unremarkable, other than a depression located 1 cm above the dentate line, accompanied by mild tenderness and a clubbed induration extending to the rectum. Colonoscopy showed a 2.0×0.8 cm longitudinal, protruding mass in the posterior wall of the lower rectum. Endosonography revealed a mixed echogenic mass originating from the rectal submucosa, with no sign of muscular wall disruption. There was no evidence of Crohn's or other diseases. Following anorectal consultation, we suspected a submucosal or internal blind fistula since the patient was symptomatic with a superficial mass which communicated to the rectum. The location and depth of the mass indicated that endoscopic resection might allow for removal of the lesion without impairment of the anorectal anatomy and function. After obtaining the patient's consent, endoscopic submucosal dissection (ESD) was performed. En bloc resection was achieved using a disposable, high-frequency knife (Micro-Tech, China). No adverse events occurred. Histopathological examination revealed a benign fistula composed of local submucous granulomatous tissue proliferation and a focal mucous epithelial defect. The patient's symptoms were relieved postoperatively, and no recurrence was evident after 6 months.

Spontaneous proximal choledochoduodenal fistula, a rare complication of cholangiolithiasis.

A 65-year-old female with a history of chronic gastritis presented with repeat epigastric pain and heartburn after meals. A physical examination was unremarkable, other than a mild fever and epigastric tenderness. Laboratory data revealed leucocytosis of 11,340/µl with 86.8 % of neutrophils, elevated γ-glutamyltransferase at 282.1 IU/l and mildly abnormal AST 40.5 IU/l, ALT 74.9 IU/l, total bilirubin 30.4 µmol/l (direct bilirubin 9.4 µmol/l) and amylase 202 IU/l. A gastroscopy showed a 4 mm fistula on the anterior wall of the proximal duodenal bulb, without ulcerations and the patient was admitted for intravenous antibiotic therapy.

A new hybrid anchoring balloon for direct peroral cholangioscopy using an ultraslim upper endoscope.

BACKGROUND AND AIM: Large impacted or residual invisible common bile duct (CBD) stones after mechanical lithotripsy are challenging. We aimed to evaluate the feasibility and success rate of a new hybrid anchoring balloon-guided direct peroral cholangioscopy (POC) for these conditions using an ultraslim endoscope. METHODS: Sixty-five patients with large or residual invisible CBD stones for direct POC from July 2012 to July 2016 were identified, including six cases in whom an additional interventional procedure was required. There were altogether 55 cases undergoing a procedure with our new device, with a 0.021-inch guidewire tied to a balloon catheter at its distal end in this single-center retrospective study. Technical success, procedure time, diagnostic and therapeutic efficacy of direct POC, and procedure-related complications were studied. RESULTS: The hybrid anchoring balloon-guided direct POC was successful in 51/55 (92.7%) procedures, including 18 cases in whom the conventional wire-guided method failed within 25 min. Mean time for technical success by our method was 12.4 ± 3.4 min. In total, of the 43 cases with previous removal of CBD stones, seven (16.3%) were found to have residual stones ≥4 mm, excluding three cases in whom direct POC failed. In another 25 cases for difficult stones, 24 lithotripsies were carried out, resulting in 23 complete fragmentations. No significant procedure-related complications were observed. CONCLUSION: The new hybrid anchoring balloon device performs well in facilitating direct POC using an ultraslim endoscope for evaluation and extraction of residual or large impacted CBD stones.

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Protective effect of Amauroderma rugosum ethanol extract and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric mucus secretions.

BACKGROUND: Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with a wide range of medicinal values. Our previous publication demonstrated the therapeutic effects of the water extract of A. rugosum (WEA) against gastric ulcers. However, the protective effects of the ethanol extract of A. rugosum (EEA) on gastric mucosa and its major active constituents have not yet been elucidated. PURPOSE: This study aims to evaluate the gastroprotective effects and underlying mechanisms of EEA and its fat-soluble constituent, ergosterol, in acute gastric ulcers. STUDY DESIGN AND METHOD: SD rats were pre-treated with EEA (50, 100, and 200 mg/kg) or ergosterol (5, 10, and 20 mg/kg), and acute gastric ulcer models were constructed using ethanol, gastric mucus secretion inhibitor (indomethacin) or pyloric-ligation. The gastric ulcer area, histological structure alterations (H&E staining), and mucus secretion (AB-PAS staining) were recorded. Additionally, Q-PCR, western blotting, immunohistochemistry, ELISA, molecular docking, molecular dynamics simulations, MM-GBSA analysis, and surface plasmon resonance assay (SPR) were used to investigate the underlying mechanisms of the gastroprotective effect. RESULT: Compared with WEA, which primarily exerts its anti-ulcer effects by inhibiting inflammation, EEA containing fat-soluble molecules showed more potent gastroprotective effect through the promotion of gastric mucus secretion, as the anti-ulcer activity was partly blocked by indomethacin. Meanwhile, EEA exhibited anti-inflammatory effects by suppressing the production of IL-6, IL-1ß, TNF-α, and NO, thereby inhibiting the MAPK pathway. Significantly, ergosterol (20 mg/kg), the bioactive water-insoluble compound in EEA, exhibited a gastroprotective effect comparable to that of lansoprazole (30 mg/kg). The promotion of gastric mucus secretion contributed to the effects of ergosterol, as indomethacin can completely block it. The upregulations of COX1-PGE2 and C-fos, an activator protein 1 (AP-1) transcription factor, were observed after the ergosterol treatment. Ergosterol acted as an LXRß agonist via van der Waals binding and stabilizing the LXRß protein without compromising its flexibility, thereby inducing the upregulation of AP-1 and COX-1. CONCLUSION: EEA and its primary bioactive compound, ergosterol, exert anti-ulcer effects by promoting gastric mucus secretion through the LXRß/C-fos/COX-1/PGE2 pathway.

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer.

Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2-related differentially expressed genes were enriched predominantly in 'chylomicron assembly', 'plasma lipoprotein particle assembly', 'high-density lipoprotein particle', 'chylomicron', 'triglyceride-rich plasma lipoprotein particle', 'very-low-density lipoprotein particle'. 'intermembrane lipid transfer activity', 'lipoprotein particle receptor binding', 'cholesterol transporter activity' and 'intermembrane cholesterol transfer activity'. In addition, 'cholesterol metabolism', and 'fat digestion and absorption' were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.

Sijunzi Decoction Targets IL1B and TNF to Reduce Neutrophil Extracellular Traps (NETs) in Ulcerative Colitis: Evidence from Silicon Prediction and Experiment Validation.

Purpose: This study was conducted to explore the mechanism of Sijunzi Decoction (SJZ) in the treatment of ulcerative colitis (UC). Methods: The study aimed to investigate the active components and targets of SJZ in the treatment of UC by screening databases such as TCMSP, GeneCards, OMIM, Distinct, TTD, and Drugbank. An online Venn tool, Cytoscape 3.7.2, and Autodock Tools were used to analyze the components and targets. The study also used a mouse model of UC to further investigate the effects of SJZ. HE staining, immunofluorescence, ELISA, qPCR, and Western blot were used to detect various indices. Results: Eighty-three active components and 112 action targets were identified from SJZ, including 67 targets for treating UC-related NETs. The five core targets identified were AKT1, JUN, IL1B, PTGS2, and TNF, and molecular docking studies indicated that the five targets were well-docked with ginsenoside Rh2, isoflavones, and formononetin. Animal experiments demonstrated that SJZ could alleviate various parameters such as weight, colon length, spleen index, disease activity index, and intestinal pathology of the UC mice. Immunofluorescence and Western blot showed that SJZ could reduce the expression of IL1B and TNF in intestinal neutrophils while increasing the expression of Occludin. Cellular immunofluorescence suggests that SJZ can reduce the expression of TNF and IL1B in NETs. The qPCR results also suggested that SJZ could inhibit TNF signal. Furthermore, ELISA results suggested that SJZ could inhibit the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) while promoting the expression of anti-inflammatory cytokines (IL-10, IL-37, TGF-ß). Conclusion: SJZ treats UC by reducing the content of intestinal NETs, with primary targets on the NETs being IL1B and TNFand suppress TNF signal. The practical components of SJZ may be ginsenoside Rh2, isoflavones, and formononetin.

Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia.

Heliobacter pylori (H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer. Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia (IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia (SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals. There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H. pylori infection.

Chemical Characterization and Metabolic Profiling of the Compounds in the Chinese Herbal Formula Li Chang Decoction by UPLC-QTOF/MS.

Background: Li Chang decoction (LCD), a Chinese medicine formula, is commonly used to treat ulcerative colitis (UC) in clinics. Purpose: This study aimed to identify the major components in LCD and its prototype and metabolic components in rat biological samples. Methods: The chemical constituents in LCD were identified by establishing a reliable ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF/MS) method. Afterwards, the rats were orally administered with LCD, and the biological samples (plasma, urine, and feces) were collected for further analyzing the effective compounds in the treatment of UC. Result: A total of 104 compounds were discriminated in LCD, including 26 flavonoids, 20 organic acids, 20 saponins, 8 amino acids, 5 oligosaccharides, 5 tannins, 3 lignans, 2 alkaloids, and 15 others (nucleosides, glycosides, esters, etc.). About 50 prototype and 94 metabolic components of LCD were identified in biological samples. In total, 29 prototype components and 22 metabolic types were detected in plasma. About 27 prototypes and 96 metabolites were discriminated in urine, and 34 prototypes and 18 metabolites were identified in feces. Conclusion: The flavonoids, organic acids, and saponins were the major compounds of LCD, and this study promotes the further pharmacokinetic and pharmacological evaluation of LCD.

Systemic injury caused by taurocholate-induced severe acute pancreatitis in rats.

Systemic injury plays a central role in severe acute pancreatitis (SAP). Retrograde biliopancreatic duct infusion of sodium taurocholate (NaT) is commonly used to establish SAP animal models. To better characterize the systemic injury in this model, SAP was induced in Sprague-Dawley rats by NaT administration (3.5 or 5%), followed by sacrifice at 3, 6, 9, 12, 24, 48 and 72 h. Normal saline was used as a control in Sham-operated rats. The mortality rate, ascites volume, and serum and ascitic fluid amylase and lipase activities were assessed. Multiple organ dysfunction, including dysfunction of the pancreas, lung, ileum, liver, and kidney, was investigated using hematoxylin and eosin staining. The interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α levels in the ascitic fluid, serum, and ileum tissues were evaluated using an enzyme-linked immunosorbent assay (ELISA). Tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in ileum tissues were studied using immunofluorescence. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE) and urea levels were measured using an automatic biochemical analyzer. The results of the present study indicated that both 3.5 and 5% NaT could induce a stable elevation of pancreatitis indices, with histopathological injury of the pancreas, lungs and ileum (5% NaT). The ascitic fluid levels of IL-6 and IL-1ß were increased in the 5% NaT group. ALT and AST levels increased temporarily and recovered in 72 h, without a significant increase in CRE and urea levels or apparent hepatic and renal pathological injury. In conclusion, rats with NaT-induced SAP have characteristics of necrotizing hemorrhagic pancreatitis with multiple organ injuries, including inflammatory lung injury, ischemic intestinal injury and slight liver and kidney injuries.

Emodin targeting the colonic metabolism via PPARγ alleviates UC by inhibiting facultative anaerobe.

BACKGROUND: Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum, which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). PURPOSE: We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora. METHODS: Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine, rosiglitazone, emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes, the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. RESULTS: Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway, emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae. CONCLUSION: The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis.

Chinese herbal compound prescriptions combined with Chinese medicine powder based on traditional Chinese medicine syndrome differentiation for treatment of chronic atrophic gastritis with erosion: a multi-center, randomized, positive-controlled clinical trial.

BACKGROUND: In this study, Chinese herbal compound prescriptions combined with Chinese medicine powder were evaluated for the treatment of chronic atrophic gastritis with erosion. METHODS: This multi-center, randomized, positive drug control clinical trial randomly assigned 216 patients with chronic atrophic gastritis with erosion to three groups: (1) control group: aluminum plus magnesium suspension thrice per day for 4 weeks; (2) test group 1: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder twice a day for 4 weeks; (3) test group 2: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder and Zhebeimu (Fritillaria thunbergii Miq.) powder twice a day for 4 weeks. The primary endpoint (improvement of gastric mucosal erosion; improvement of gastric mucosal pathology) and secondary endpoints (improvement of clinical symptoms scores; improvement of the patient-reported outcome [PRO] instrument for chronic gastrointestinal diseases) were assessed using endoscopy at week 4 following the treatment. Drug-related adverse events (AEs) and adverse drug reactions (ADRs) were also compared. RESULTS: The final analysis included 202 patients (control group, 63; test group 1, 69; test group 2, 70). At week 4, using within-group comparison, gastric mucosal erosion improved in each group following treatment with a significant difference (P < 0.05); there were no statistically significant differences in gastric mucosal erosion scores among the groups after treatment (P > 0.05); in terms of improvement of gastric mucosal erosion, the efficacy rate of the control group was 69.12%, the efficacy rate of the test group 1 was 73.24%, and the efficacy rate of the test group 2 was 69.01% and efficacy rate among the groups was not statistically significant (P > 0.05). As determined by acute inflammation, chronic inflammation, atrophy, intestinal metaplasia, and dysplasia, the pathological score (total score and the highest score) did not differ statistically among groups following treatment (P > 0.05); within the control group, the total scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); in the test group 1, chronic inflammation, atrophy, and intestinal metaplasia and dysplasia scores were significantly decreased (P < 0.05), but acute inflammation did not improve (P > 0.05); there was a significant reduction in the atrophy score in test group 2 (P < 0.05), but no improvement in the scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Similarly, within the control group, the highest scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); there was a significant reduction in highest scores of atrophy, intestinal metaplasia, and dysplasia (P < 0.05) in test group 1, but the highest scores didn't not improve with acute inflammation and chronic inflammation (P > 0.05); there was a significant reduction in the highest atrophy score in test group 2 (P < 0.05), but no improvement in the highest scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Compared to the control group, the main symptom scores and total symptom scores in the test groups were lower following treatment, with a statistically significant difference (P < 0.05); the analysis of covariance with center, erosion type, and group as factors was applied, and the comparison among the groups in dyspepsia, defecation, and total PRO instrument scores were statistically significant (P < 0.05). In the study period, AEs were reported in 3 (4.23%) patients in the test group 1 and 3 (4.41%) patients in the control group; ADRs were confirmed in 3 (4.23%) patients from the test group 1 and 2 (2.94%) from the control group. AEs and ADRs were not statistically significantly different among groups (AE, P = 0.2213; ADR, P = 0.2872). No serious AE or ADR was reported. CONCLUSIONS: This study has shown that both aluminum plus magnesium suspension and Chinese herbal compound prescriptions together with Panax notoginseng powder are capable of improving gastric mucosal erosion and reducing gastric mucosal pathological scores, and there were no statistically significant differences among the groups in primary endpoints, indicating that Chinese herbal therapy can achieve similar efficacy than antacids in terms of primary outcomes. The aluminum plus magnesium suspension is comparable to Chinese herbal therapy in improving atrophy and intestinal metaplasia, and is inferior to Chinese herbal therapy in improving dysplasia. In addition, the Chinese herbal therapy significantly outperforms the aluminum plus magnesium suspension in improving symptoms. Therefore, the overall clinical outcome of Chinese herbal compound prescriptions together with Panax notoginseng powder based on TCM syndrome patterns in the treatment of erosive gastritis is superior to that of antacids. Trial registration ChiCTR, ChiCTR-IPR-15005905. Registered 22 January 2015, https://www.chictr.org.cn/showproj.aspx?proj=10359.

Clinical Strains of Helicobacter pylori With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy.

Helicobacter pylori was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of H. pylori activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular H. pylori and promotes its drug resistance. This study revealed that some clinical drug-resistant H. pylori strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from Pogostemon cablin (Blanco) Benth (Labiatae), showed reliable activity against intracellular H. pylori. The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by H. pylori, thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular H. pylori has great implications for clinical treatment, and PA can act against invasive H. pylori based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant H. pylori.

Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of Helicobacter pylori.

The long-term colonization of Helicobacter pylori can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of H. pylori. Patchouli alcohol (PA) shows a highly efficient activity against H. pylori in vitro and in vivo. And this study aims to explore whether PA can reduce the resistance of H. pylori and determine the underlying mechanism. Checkerboard and time-kill bactericidal curve assay reveal that the combination of PA and clarithromycin (CLR) promoted the inhibition and bactericidal effect against H. pylori. Stimulation of CLR leads to the internalization of H. pylori, but PA can effectively inhibit the invasion induced by CLR. Compared with antibiotics, PA remarkably eradicated the intracellular H. pylori, and this intracellular sterilized ability was further improved in combination with antibiotics (CLR and metronidazole). The expression of H. pylori efflux pump genes (hp0605, hp1327, and hp1489) was dose-dependently downregulated by PA. Digital droplet PCR indicated that the H. pylori mutant of A2143G can be inhibited by PA. Cellular uptake and transport assays showed that PA is rapidly absorbed, which promotes its activity against intracellular bacteria. Therefore, PA can act synergistically with CLR as a candidate treatment against drug-resistant H. pylori.

Novel peroral cholangioscopy-directed lithotripsy using an ultraslim upper endoscope for refractory Mirizzi syndrome: A case report.

RATIONALE: Mirizzi syndrome (MS) is an uncommon condition characterized by common hepatic duct (CHD) compression by an impacted gallbladder or cystic duct stones or adjacent inflammation. To date, a standardized therapeutic strategy for MS has not been established yet, owing to its complex clinical presentation. Thus, researchers still have to develop new optimized approaches to solve this problem. Herein, we describe a patient with refractory MS who underwent a successful treatment by novel hybrid anchoring balloon-guided direct peroral cholangioscopy (POC) using an ultraslim endoscope. PATIENT CONCERNS: A 56-year-old man with a history of biliary stone was referred to our hospital for complaints of discomfort in the right upper quadrant of the abdomen and obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed an 18-mm impacted stone at the level of the cystic duct, which compressed the CHD. The CHD had local stricture, with its upstream and intrahepatic bile duct dilation. DIAGNOSES: He was diagnosed with type I MS. INTERVENTIONS: Initially, the patient received an endoscopic major sphincterotomy. However, conventional stone extraction, including mechanical lithotripsy, was unsuccessful. Then, after signing the informed consent form for further treatment, he was successfully treated with novel hybrid anchoring balloon-guided direct POC. OUTCOMES: The patient had no operative complications and was discharged with cleared ducts. At the 3-year follow-up, he was asymptomatic. LESSONS: Our novel hybrid anchoring balloon-guided direct POC may be an effective alternative treatment approach for difficult gallbladder cases, such as refractory MS.

Exploration in the Mechanism of Kaempferol for the Treatment of Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. METHODS: The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. RESULTS: A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. CONCLUSIONS: This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.

Study on the Mechanism of Olfactomedin 4-shRNA Plasmid Chitosan Magnetic Nanoparticles in Intestinal Metaplasia of Chronic Atrophic Gastritis.

Intestinal metaplasia (IM) refers to the replacement of gastric epithelial cells by intestinal epithelial cells. This is often accompanied by chronic atrophic gastritis (CAG), which is a precancerous lesion of gastric cancer. The incidence rates of CAG and IM are increasing gradually, which generates an enormous economic burden to individuals and society. To explore the pathogenesis of CAG with IM, we screened out the differentially expressed gene olfactomedin 4 (OLFM4) by bioinformatics and constructed OLFM4-shRNA plasmid chitosan magnetic nanoparticles to knockdown this gene. This caused a downregulation of caudal type homeobox 2 (CDX2), a marker of IM, suggesting that knocking down OLFM4 may slow the pathological process of IM, thus providing putative relevant targets for the treatment of CAG with IM.