Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Serum food specific IgG antibodies are associated with small bowel inflammation in patients with Crohn's disease.

BACKGROUND/AIMS: Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn's disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients. METHODS: We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score. RESULTS: Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively). CONCLUSION: Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.

Optimal frequency determination for terahertz technology-based detection of colitis-related cancer in mice.

Colorectal cancer is a prevalent malignancy globally, often linked to chronic colitis. Terahertz technology, with its noninvasive and fingerprint spectroscopic properties, holds promise in disease diagnosis. This study aimed to explore terahertz technology's application in colitis-associated cancer using a mouse model. Mouse colorectal tissues were transformed into paraffin-embedded blocks for histopathological analysis using HE staining. Terahertz transmission spectroscopy was performed on the tissue blocks. By comparing terahertz absorption differences, specific frequency bands were identified as optimal for distinguishing cancerous and normal tissues. The study revealed that terahertz spectroscopy effectively differentiates colitis-related cancers from normal tissues. Remarkably, 1.8 THz emerged as a potential optimal frequency for diagnosing colorectal cancer in mice. This suggests the potential for rapid histopathological diagnosis of colorectal cancer using terahertz technology.

Integrated bioinformatics analysis for conducting a prognostic model and identifying immunotherapeutic targets in gastric cancer.

BACKGROUND: Gastric cancer is the third leading cause of death from cancer worldwide and has a poor prognosis. Practical risk scores and prognostic models for gastric cancer are lacking. While immunotherapy has succeeded in some cancers, few gastric cancer patients benefit from immunotherapy. Immune genes and the tumor microenvironment (TME) are essential for cancer progression and immunotherapy response. However, the roles of immune genes and the tumor microenvironment in immunotherapy remain unclear. The study aimed to construct a prognostic prediction model and identify immunotherapeutic targets for gastric cancer (GC) patients by exploring immune genes and the tumor microenvironment. RESULTS: An immune-related risk score (IRRS) model, including APOH, RNASE2, F2R, DEFB126, CXCL6, and CXCL3 genes, was constructed for risk stratification. Patients in the low-risk group, which was characterized by elevated tumor mutation burden (TMB) have higher survival rate. The risk level was remarkably correlated with tumor-infiltrating immune cells (TIICs), the immune checkpoint molecule expression, and immunophenoscore (IPS). CXCL3 and CXCL6 were significantly upregulated in gastric cancer tissues compared with normal tissues using the UALCAN database and RT-qPCR. The nomogram showed good calibration and moderate discrimination in predicting overall survival (OS) at 1-, 3-, and 5- year for gastric cancer patients using risk-level and clinical characteristics. CONCLUSION: Our findings provided a risk stratification and prognosis prediction tool for gastric cancer patients and further the research into immunotherapy in gastric cancer.

Clinical characteristics and quality of life in patients with inflammatory bowel disease-associated anemia in Southeast China.

BACKGROUND/AIMS: Clinical characteristics of inflammatory bowel disease (IBD) with anemia have not been fully elucidated. This study aimed to investigate the frequency of, risk factors for, and management of anemia in IBD patients and to evaluate the quality of life (QOL) in IBD patients with anemia. METHODS: We included two patient cohorts. In cohort 1, clinical data from 697 IBD patients were retrospectively collected. In cohort 2, the Short Form-36 Health Survey (SF-36) and Fatigue Scale-14 (FS-14) questionnaires for IBD patients were completed to evaluate the QOL. RESULTS: Anemia was present in 35.6% of IBD patients [38.2% of Crohn's disease (CD) patients vs. 29.3% of ulcerative colitis (UC) patients, P = 0.025]. Elevated platelet (PLT) count (CD: OR, 1.004; 95% CI, 1.001-1.007; P = 0.007; UC: OR, 1.010; 95% CI, 1.004-1.016; P = 0.001), elevated erythrocyte sedimentation rate (ESR) (CD: OR, 1.024; 95% CI, 1.012-1.036; P < 0.001; UC: OR, 1.025; 95% CI, 1.001-1.051; P = 0.044), and lower albumin levels (CD: OR, 0.801; 95% CI, 0.749-0.857; P < 0.001; UC: OR, 0.789; 95% CI, 0.720-0.864; P < 0.001) were associated with anemia. Among the IBD patients with anemia, only 25.8% received treatment for anemia. IBD patients with anemia had significantly lower SF-36 scores (P = 0.011) and higher FS-14 scores (P = 0.026) than those without anemia. CONCLUSION: Anemia is common in IBD patients. Elevated PLT count and ESR are risk factors for anemia in IBD patients. Anemia may negatively impact IBD patients' QOL, but few anemia patients receive treatment for anemia.

Cronkhite-Canada syndrome: a retrospective analysis of four cases at a single medical center.

OBJECTIVE: Cronkhite-Canada syndrome (CCS) is a rare disease that is characterized by multiple gastrointestinal polyps and ectodermal abnormalities. This study aimed to improve the understanding of CCS by presenting our patient data. METHODS: Clinical features, treatment, and outcomes of four CCS patients at a single medical center were retrospectively analyzed. RESULTS: The age of the patients ranged from 32 to 61 years (mean: 49.5 years), including three men and one woman. All the patients presented with gastrointestinal symptoms, ectodermal abnormalities, and multiple gastrointestinal polyps. Two patients showed abnormal immune indices. Three patients underwent magnetic resonance enterography, and the typical manifestations of small intestine involvement were diffuse wall thickening, high signal intensity on diffusion-weighted imaging, obvious enhancement, and multiple small nodular enhancements of the small intestine. The main histological manifestations were chronic inflammation and hyperplastic, adenomatoid, and hamartomatoid polyps. Eosinophilic infiltration was observed in two patients. One patient had rectal adenocarcinoma at the time of diagnosis. All the four patients received prednisone at a dose of 0.75-1 mg/kg/day, and had their gastrointestinal symptoms gradually resolved (including two with ectodermal abnormality and endoscopic remission). Two patients are currently receiving low-dose prednisone (2.5-5 mg/day) with no recurrence after a 1.5- and 6-year follow-up periods, respectively. CONCLUSION: Magnetic resonance enterography has the potential to evaluate small-intestinal lesions in CCSs. Long-term therapy with low doses of prednisone may be beneficial in maintaining remission.

Association between ABO blood group and risk of Crohn's disease: A case-control study in the Chinese Han population.

BACKGROUND: Blood group O has been reported to be a potentially protective factor for Crohn's disease (CD) susceptibility in Caucasian and Korean populations, but a similar conclusion was not found in a Chinese study. The present study investigated the potential association in the Chinese Han population. METHODS: We included 275 CD patients, 132 ulcerative colitis (UC) patients and 1201 healthy individuals in this case-control study. The demographic characteristics and ABO blood group were compared among the three groups. The clinical characteristics and treatment of CD were further investigated according to the blood group distribution. RESULTS: The blood group distribution in CD patients was significantly different from healthy controls, and the frequency of O blood in CD patients was significantly lower compared to healthy controls. After adjusting for age and gender, the non-O blood groups remained significantly associated with CD susceptibility in propensity score-adjusted and propensity score-matched analyses. Compared to CD patients with non-O blood groups, patients with O blood were at a lower risk of developing penetrating disease, more likely to receive immunosuppressant treatment and less likely to receive biological treatment. CONCLUSION: Our results confirmed that non-O blood groups were significantly associated with an increased risk of CD in the Chinese Han population.

Integrative analyses identified ion channel genes GJB2 and SCNN1B as prognostic biomarkers and therapeutic targets for lung adenocarcinoma.

OBJECTIVES: Abnormal expressions of ion channel genes are associated with the occurrence and progression of tumors. At present, their roles in the carcinogenesis of lung adenocarcinoma (LUAD) are not clear. MATERIALS AND METHODS: Differentially expressed (DE) genes in the tumorigenesis were identified from 328 ion channel genes in 102 LUAD and paired adjacent normal samples. Similar analyses were performed between 177 metastatic and 286 non-metastatic LUAD samples to identify DE ion channel genes in the progression of LUAD. Independent prognostic factors selected from DE ion channel genes were used to construct a prognostic model. Correlation analysis and drugs-drug targets interaction network were used to screen the potential drugs for LUAD patients stratified by GJB2 or SCNN1B. RESULTS: Six ion channel genes (GJB2, CACNA1D, KCNQ1, SCNN1B, SCNN1G and TRPV6) were continuous differentially expressed in the tumorigenesis and progression of LUAD. The survival analysis in four datasets with 522 LUAD samples showed that GJB2 and SCNN1B were independent prognostic biomarkers. Patients with overexpression of GJB2 or underexpression of SCNN1B had shorter overall survival. Moreover, multi-omics analysis showed that hypomethylation of GJB2 and hypermethylation of SCNN1B in the promoter region may contribute to their aberrant expressions. KEGG enrichment analysis showed that the overexpressed genes in the group with high GJB2 or low SCNN1B were enriched in cancer-related pathways, while the underexpressed genes were enriched in metabolism-related pathways. The prognostic model with GJB2 and SCNN1B can stratify all LUAD patients into two groups with significantly different survival. Correlation analysis and drugs-drug targets interaction network suggested that GJB2 and SCNN1B expression might have indicative therapeutic values for LUAD patients. Finally, pan-cancer analysis in other eight cancer types showed that GJB2 and SCNN1B might be also potential prognostic factors for KIRC. CONCLUSIONS: GJB2 and SCNN1B were identified as prognostic biomarkers and therapeutic targets for LUAD.

Genetic variants of autophagy-related genes in the PI3K/Akt/mTOR pathway and risk of gastric cancer in the Chinese population.

OBJECTIVE: Autophagic dysfunction could lead to tumorigenesis and affect tumor progression and prognosis. The PI3K/Akt/mTOR signaling pathway plays an important role in autophagy. The aim of the studies was to explore the association between genetic variants of autophagy-related genes in the PI3K/Akt/mTOR pathway and gastric cancer risk. METHODS: We selected candidate genes via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO), then used Ensemble, HaploView, and 1000 Genomes Project datasets to extract single nucleotide polymorphisms (SNPs) in the candidate genes. We screened the differently distributed SNPs in 96 gastric cancer patients and 96 healthy controls as candidate SNPs using SNP Array and verified the candidate SNPs in 622 patients and 622 healthy controls using time-of-flight mass spectrometry. RESULTS: Candidate SNPs located in, IRS1 (rs10205233 C > T), PIK3CD (rs3934934 A > G), PIK3R1 (rs706711 A > G), and AKT1 (rs35285446 ->T), were selected. IRS1 (rs10205233 C > T) was significantly associated with gastric cancer risk (adjusted OR = 0.76, 95%CI = 0.59-0.97, p = 0.031 in co-dominant model; adjusted OR = 0.76, 95%CI = 0.60-0.97, p = 0.029 in dominant model). There were no significant associations between the rest of candidate SNPs and gastric cancer risk. CONCLUSION: The IRS1 (rs10205233 C > T) could be a specific biomarker for gastric cancer patients in Xianyou County, a rural area with a high prevalence of gastric cancer in Fujian Province.

Optical coherent tomography to evaluate the degree of inflammation in a mouse model of colitis.

BACKGROUND: There is an urgent need to develop a noninvasive imaging technique for the diagnosis of early inflammatory lesions or early and real-time microscopic assessment before selecting the most representative biopsy sites. METHODS: In this study, a dextran sulfate sodium colitis model was developed, and intestinal histological damage scores measured the degree of inflammation in colitis. According to these scores, 6 parameters were designed for hematoxylin and eosin (HE) sections based on morphological changes, and 2 parameters were designed for optical coherence tomography (OCT) images to measure submucosal edema by morphological changes to evaluate inflammation degrees in the colon. Spearman's rank correlation method was used to compare the correlation between the submucosal morphological changes and the different degrees of inflammation. One-way analysis of variance (ANOVA) was used for comparisons among groups, while receiver operating characteristic (ROC) curves of the indicators in HE sections and OCT images were plotted. RESULTS: In HE sections, angle of mucosal folds (r=0.853, P<0.01), length of basilar parts (r=0.915, P<0.01), submucosal area (r=0.819, P<0.01), and height between submucosal and muscular layers (r=0.451, P=0.001) were correlated with the degree of inflammation in colitis. In OCT images, length of basilar parts (r=0.800, P<0.01) and height of submucosa + thickness of muscularis (r=0.648, P=0.001) were correlated with the degree of inflammation and aided the measurement of inflammation in the colon. CONCLUSIONS: Parameters based on morphological changes in OCT images and HE sections were significant indexes for evaluating the degree of inflammation in colitis. OCT images have advantages for future clinical applications in situ, including noninvasiveness and real-time imaging.

Effects of pentasa-combined probiotics on the microflora structure and prognosis of patients with inflammatory bowel disease.

BACKGROUND/AIMS: The aim of the present study was to investigate the effects of the combination treatment of pentasa and probiotics on the microflora composition and prognosis in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: A total of 40 patients with IBD (19 control group and 21 observation group) were randomized. Patients in the control group were given pentasa, and patients in the observation group were given probiotics along with pentasa. The microflora composition, biochemical indices, inflammatory markers, and activity scores of the two groups were analyzed. RESULTS: After treatment, the number of enterobacteria, enterococci, saccharomyces, and bacteroides; the levels of fecal lactoferrin, 1-antitrypsin, ß2-microglobulin, high-sensitivity C-reactive protein, and interleukin (IL)-6; activity scores; and recurrence rate in the observation group were significantly lower than those in the control group. Bifidobacterium and lactobacillus counts and IL-4 levels were significantly higher in the observation group than in the control group. CONCLUSION: The combination of probiotics and pentasa can improve microflora composition in patients with IBD and reduce the level of inflammatory cytokines; therefore, it is worthy of further clinical validation.

Melatonin alleviates circadian rhythm disruption exacerbating DSS-induced colitis by inhibiting the distribution of HMGB1 in intestinal tissues.

Circadian rhythm disruption (CRD) is regarded as a risk factor for inflammatory bowel disease (IBD), and it was reported to suppress the level of melatonin, which execute anti-inflammatory effects. High mobility group box 1 protein (HMGB1) is a member of the damage-associated molecular pattern (DAMP) family and has been verified as an IBD-associated inflammatory cytokine that mediates the TLR4-NF-κB pathway. However, no exact mechanism has been illustrated among melatonin, disrupted circadian rhythm and inflammatory bowel disease, as well as regarding the effect of melatonin on HMGB1. In the present study, we aimed to explore the role of relationship with HMGB1. CRD aggravated DSS-induced colitis by worsening colonic inflammation and tissue injury, as well as by enhancing HMGB1 translocation, which could be reversed by ethyl pyruvate, an HMGB1 antagonist. Moreover, melatonin treatment attenuated these disorders and the shuttling of HMGB1 in the intestinal epithelial cells (IECs), the effect of which could be partly reversed by the melatonin antagonist luzindole. The protective role of melatonin may be tightly related to the translocation of HMGB1 in IECs. Accordingly, these results suggested that melatonin may be a new therapeutic beneficial option in IBD patients, especially for those with circadian rhythm disruption.

Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis.

BACKGROUND: Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients with moderate-to-severe and steroid-refractory UC. METHODS: A literature search identified studies that investigated tacrolimus and IFX in moderate-to-severe steroid-refractory patients with UC. The primary outcome was short-term clinical response to treatment, including the remission and response rates. Secondary outcomes included the rates of colectomy at 3 months and adverse events rate. RESULTS: A total of 6 studies comprising 438 cases were eligible for inclusion. The pooled analysis showed that the short-term clinical response rate, clinical remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%, respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%, respectively, for those receiving IFX. No significant difference was, however, seen for tacrolimus compared with IFX with regard to clinical remission rate (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67), clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P = .006). CONCLUSIONS: Our meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for these patients.

Enho Mutations Causing Low Adropin: A Possible Pathomechanism of MPO-ANCA Associated Lung Injury.

BACKGROUND: Myeloperoxidase (MPO) anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis commonly causes life-threatening pulmonary alveolar hemorrhage or fibrosis. Only a limited number of candidate gene variants have been explored, but hitherto, are not widely confirmed. In the present study, we investigated the importance of energy homeostasis associated gene (Enho) mutations and adropin deficiency in the development of MPO-ANCA associated lung injury. METHODS: We analyzed the peripheral blood mononuclear cells from 152 unrelated patients and 220 population-matched healthy individuals for genetic variations in Enho. Functional studies with adropin knockout (AdrKO) on C57BL/6J mice were also performed. FINDINGS: Sequencing revealed six patients with p.Ser43Thr and that five patients shared Cys56Trp amino acid substitution in Enho. Serum concentration of adropin was significantly lower in patients than that of the healthy subjects (P<0.0001), especially those with Enho mutations. In vivo, homo- and heterozygous carriers of the null adropin allele exhibited MPO-ANCA associated pulmonary alveolar hemorrhage as compared to wild-type mice. AdrKO mice exhibit reduced eNOS (Ser1177) and Akt1 (Ser473) phosphorylation and loss of Treg cells. INTERPRETATION: Our findings indicate that the presence of Enho mutations or adropin-deficiency is a probable molecular basis for the initial events triggered in MPO-ANCA associated lung injury.

[Changes of colonic permeability and its correlation with TNF-α, NF-κB p65 in ulceration colitis mice].

OBJECTIVE: To study the changes of colonic permeability and its correlation with TNF-α, NF-κB p65 in indextran sulphate sodium (DSS) -induced ulcerative colitis(UC) of mice. METHODS: Forty-eight ICR mice were randomly divided into the control group and the model group. The acute UC model was induced by quantified intragastric administration of 2.5% DSS in mice. The disease activity index(DAI), histopathology scores, colonic permeability, expression of TNF-α, NF-κB p65 in colonic tissue were determined. The change of colonic permeability and its correlation with DAI, TNF-α, NF-κB p65 were analyzed. RESULTS: Compareded with the control group, DAI colonic permeability of colonic tissue,and the expression of TNF-α NF-κB p65 in the model group were increased significantly (P<0.01, P<0.01). The increased colonic permeability correlated with DAI (P<0.01), and the expression of TNF-α(P<0.01), NF-κB p65(P<0.01) changed significantly. CONCLUSIONS: The alteration of colonic permeability and increased expression of TNF-α, NF-κB p65 may play important roles in the occurrence and development of UC.

Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer.

BACKGROUND: Highly sensitive markers are urgently needed for the diagnosis and grading of gastric cancer and for managing drug resistance. The recent identification of long-non-coding RNAs (lncRNAs) has provided new approaches for resolving this challenge. The aim of this study was to screen and identify new biomarkers for human gastric cancer from lncRNAs. METHODS: First, we used lncRNA microarrays to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in both human gastric cancer tissues and in two gastric cancer cell lines, SGC7901 cells and paclitaxel-resistant SGC7901 cells. The lncRNA plasma-cytoma variant translocation 1 (PVT1) was found to exhibit higher expression in both gastric cancer tissues and the SGC7901 paclitaxel-resistant cell line. Quantitative polymerase chain reaction was used for large-scale analysis in a large number of human gastric cancer tissues to verify the involvement of PVT1 in development of gastric cancer. The relationships between PVT1 expression and clinical features were also analyzed. RESULTS: PVT1 showed higher expression in human gastric cancer tissues than in adjacent non-cancerous tissues and in SGC7901 paclitaxel-resistant cells compared with SGC7901 cells. PVT1 expression was correlated with lymph node invasion of gastric cancer. CONCLUSION: PVT1 is a new biomarker for human gastric cancer and may indicate lymph node invasion. Therefore, PVT1 shows potential as a novel therapeutic target for the treatment of gastric cancer and enhancement of paclitaxel sensitivity.