Detecting and demarcating early gastric cancers (EGC) after eradication therapy of Helicobacter pylori (H. pylori) is a challenging task due to the fact that the lesion’s surface is covered with gastritis-like tissue (non-neoplastic epithelium covering the cancerous tissue). However, our study aimed to investigate the endoscopic alterations of EGC within 3 months after eradication, which has not been reported clearly yet. Consecutive EGC patients who underwent two gastroscopies (one with H. pylori infection and another within 3 months after successful H. pylori eradication) were enrolled. The endoscopic photographs were evaluated for the endoscopic features and confidence level of demarcation line (DL), invasion depth, and histopathological classification by three highly experienced endoscopists. The DL estimated by endoscopy was compared with that of postoperative pathological examination. 45 pairs of EGC cases before and after eradication were enrolled. All the confidence level of DL (High confidence: 15.6

Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8’s role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients’ data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3β from the Wnt/β-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven β-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3β, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.

BackgroundMacrophages exhibit different phenotypes in inflammatory bowel disease (IBD) and promote inflammation or tissue repair depending on their polarization state. Alcohol is a widely used solvent in pharmaceutical formulations, and its consumption is associated with an increased risk of colitis; however, its effects on macrophages in IBD remain poorly understood.PurposeThis study aimed to investigate the effect of alcohol on macrophages in dextran sodium sulfate (DSS)-induced colitis and understand the underlying mechanisms.MethodsDSS-treated C57BL/6 mice were exposed to varying concentrations of alcohol, transient receptor potential vanilloid 1 (TRPV1) antagonist, and 5-aminosalicylic acid. The distal colon was resected, fixed, stained, and histologically analyzed, through hematoxylin and eosin (H&E) staining and immunofluorescence staining. Ratio [Ca2+]i measurements, western blotting, quantitative polymerase chain reaction, cytokine measurements, and RNA sequencing analyses were also performed. Peritoneal macrophages and RAW264.7 cells were used for in vitro experiments, and various assays were performed to evaluate cellular responses, gene expression, and signaling pathways.ResultsAlcohol exacerbated DSS-treated mice colitis and promoted the secretion of various inflammatory cytokines from colonic macrophages. Alcohol enhances the calcium ion influx induced by lipopolysaccharide (LPS) in peritoneal macrophages, while the TRPV1 antagonist capsazepine (CPZ) inhibits LPS- and/or alcohol- induced calcium influx in macrophages. Alcohol and LPS activate the MAPK/P38, MAPK/ERK, and NF-κB signaling pathways and induce the macrophage M2b polarization, resulting in the increased expression level of inflammatory cytokines such as Tnf, Il1b, and Il10. Additionally, CPZ can inhibit the facilitatory effects of alcohol or LPS on the abovementioned pathways and inflammatory factors, reversing macrophage M2b polarization and promoting alcohol-induced colitis. The inhibition of nucleotide binding oligomerization domain containing 2 (NOD2) partially suppressed the alcohol and LPS effects on macrophages.ConclusionAlcohol exacerbates experimental colitis and induces M2b polarization of macrophage via TRPV1-MAPK/NF-κB. Our study provides new insights into the potential therapeutic targets for IBD treatment by elucidating the role of TRPV1 in alcohol-exacerbated colitis, using CPZ as a potential therapeutic option. The identification of transient receptor potential ankyrin subtype 1 (TRPA1) as a therapeutic target expands the scope of future research.

Background: N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD. Methods: The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry. Results: In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells. Conclusion: A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.

急性消化道出血是常见的急症,包括急性非静脉曲张性上消化道出血、急性食管胃静脉曲张出血和急性下消化道出血.急诊内镜在急性消化道出血中起着重要作用,而急诊内镜的时机一直存在争议.本文就急性消化道出血急诊内镜的时机及内镜下治疗方式等作一综述.

Background There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFT R) technique for GISTs.Methods In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. Results The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were dis -charge d within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant me-tastas is.Conclusions NT-EFTR was a feasible method for the resec-tion of gastric GISTs and can be expected to achieve com-plete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural diffi-culty.

Background Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. Methods Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan–Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. Results LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells (P < 0.01), elevated SW480 cells sensitivity to 5-FU (P < 0.01), reduced LC3 punctate aggregates (P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 (P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. Conclusion LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.

METHODS:This retrospective study enrolled 65 achalasia patients who underwent POEM from June 2017 to October 2021. Based on the preoperative diet strategies, patients were divided into carbonated beverage group (n = 48) and control group (n = 17). Demographic and clinical data, duration of preoperative endoscopy, quality of esophagus cleansing, and patient satisfaction on preoperative procedure were collected and compared. In the current study, we established the quality of esophagus cleansing: Grade A, no remnants or only liquid or frothy discharge; Grade B, a little amount of solid content remained; and Grade C, a large amount of solid content remained.RESULTS:There were 41 Grade A, 6 Grade B, and 1 Grade C patients in the carbonated beverage group, while there were 8 Grade A, 6 Grade B, and 3 Grade C patients in the control group (p value = 0.001). The esophagus cleansing degrees were significantly ameliorated after drinking carbonated beverages in all the three subtypes of achalasia according to the degree of dilatation. The mean duration of preoperative endoscopy was 6.54 ± 2.250 minutes in the carbonated beverage group and 10.27 ± 4.788 minutes in the control group (p value = 0.010). The score of patient satisfaction concerning the procedure before the POEM in the carbonated beverage group was 4.5 ± 0.652, while the score in the control group was 4.35 ± 0.702 (p value = 0.436). In the multivariate analysis, patient satisfaction was significantly associated with male (odds ratio 0.296, 95% CI: 0.097-0.905, p value = 0.033).CONCLUSIONS:Drinking carbonated beverages reduce the duration of preoperative endoscopy and ameliorate the esophagus cleansing degrees without impairing patient satisfaction.

Background:Transient receptor potential channels are the major temperature and nociceptive receptors in the human body and transient receptor potential melastatin 8 (TRPM8) is the cold-sensitive and non-selective cation channel. In our study, we performed a bibliometric analysis of TRPM8 from 2002 to 2021 to summarize the current research status and potential research direction in the future.Methods:The TRPM8-related publications were selected from the Web of Science Core Collection SCI-EXPANDED database from 2002 to 2021. The publication details, such as authors, titles, and author keywords, were used for bibliometric analysis and network visualization to present the current state of TRPM8 research.Results:A total of 1035 articles met the inclusion criteria. The number of TRPM8-related articles has grown rapidly over the past two decades. The USA has the largest number of publications, citations, and international collaborations. The TRPM8-related articles are mainly published and cited in neurological journals, such as the Journal of Neuroscience (41 publications and 2171 local citations). Prevarskaya N. has the most publications (26), and Patapoutian A. has been cited the most (1414 local citations). The popular disciplines in TRPM8 research include Neurosciences and Neurology, Pharmacology and Pharmacy, Biochemistry, and Molecular Biology. Research hotspots are mainly TRP channel, calcium, prostate cancer, proliferation, pain, cold, nociception, and inflammation.Conclusion:Our bibliometric analysis demonstrates that the number of TRPM8 studies has increased from 2002 to 2021. The global research trends and hotspots include the activation mechanism of TRPM8 in neurons, the role of TRPM8 in neuronal and non-neuronal diseases, and therapeutic target research.

Abstract Background There has always been a debate on the optimal timing of endoscopy in patients with acute variceal bleeding (AVB). Objective This study aimed to examine the relation between the timing of endoscopy and the short-term outcomes of patients with AVB. Methods Patients with AVB who underwent endoscopy within 24 h after admission at our tertiary care center from 2014 to 2022 were evaluated retrospectively. The primary outcomes were the 6-week mortality and re-bleeding. The secondary outcomes included the total number of blood units transfused, the length of hospital stay, and the need for salvage therapy. We used Cox proportional hazards model to analyze the predictors of 6-week mortality in all patients as well as in those who were at high risk of further bleeding or death. Results A total of 312 patients were enrolled. Among them, 170 patients (54.49%) underwent urgent endoscopy (< 6 h), and 142 patients (45.51%) underwent early endoscopy (6–24 h). There were no significant differences between the urgent-endoscopy group and the early-endoscopy group, regarding the 6-week mortality (16.47% vs. 10.56%; P value = 0.132) and 6-week re-bleeding rate (11.2% vs. 16.2%; P value = 0.196). In multivariate analysis, time to endoscopy was independent of 6-week mortality (P value = 0.170), but the time between the beginning of bleeding and endoscopy (within 12 h) was significantly associated with low 6-week mortality (OR: 0.16; 95% CI: 0.06–0.46; P value = 0.001). Time to endoscopy was still not associated with 6-week mortality in patients at high risk for further bleeding or death (Glasgow-Blatchford score ≥ 12, n = 138, P value = 0.902). Conclusions Endoscopy performed within 6 h of admission, rather than within 6 to 24 h, did not improve six-week clinical outcomes in patients in stable condition with AVB and even those who were at high risk of further bleeding and death.

AIM:To explore the endoscopic features and risk factors of early gastric cancer (EGC) after eradication of Helicobacter pylori (H. pylori).METHODS:A total of 1961 patients who underwent esophago-gastro-duodenoscopy (EGD) with a history of successful H. pylori eradication were enrolled in this multicenter research. Among them, 162 EGC lesions of 132 patients were detected. The endoscopic features and risk factors of post-eradication EGC were explored.RESULTS:Severe atrophy (75.3% vs. 16.7%, p value <.01), intestinal metaplasia (96.3% vs. 77.1%, p value <.01), map-like redness (89.5% vs. 65.4%, p value <.01), distinct intermediate zone (IZ) (68.5% vs. 23.4%, p value <.01) and xanthoma (58.0% vs. 17.9%, p value <.01) were significantly more frequent in the CA group (patients with newly detected EGC after eradication of H. pylori) than in the NC group (patients without gastric cancer after eradication of H. pylori). In multivariate analysis, severe atrophy (odds ratio (OR) = 8.08; 95% confidence interval (CI), 3.43-20.0; p value<.01), map-like redness (OR = 1.75; 95% CI, 0.11-5.25; p value = .04), distinct IZ (OR = 2.87; 95% CI, 1.20-6.93; p value = .02) and xanthoma (OR = 2.84; 95% CI, 1.20-7.03; p value=.02) were proved to be risk factors for detection of EGC after eradication of H. pylori.CONCLUSIONS:Severe atrophy and map-like redness and distinct IZ and xanthoma are risk factors of EGC after eradication of H. pylori.

类风湿关节炎(rheumatoid arthritis ,RA )是一种以侵蚀性关节炎为特点的自身免疫性疾病,具有高致残率.RA的全球患病率为0 .5％ ～1％[1] ,中国大陆地区为0 .42％,总患病例数为500多万.该病严重影响患者生活质量,消耗医疗资源,给社会带来沉重负担[2 ].

BackgroundWith a shift in the healthcare paradigm towards a more patient-centered approach, data on inflammatory bowel disease (IBD) needs to be further explored. This study aimed to determine patient perspectives on the effect of IBD and features of patients with lower satisfaction level and compare patient and physician perception of IBD-related Quality of Care (QoC).MethodsA previously developed pre-standardised set of questions regarding patient-centered outcome (PRO) measures for IBD, comprising 36 items, was administered in five centers, and a concomitant questionnaire for specialised physicians was adapted and administered.ResultsOverall, 1005 patients with IBD met the inclusion criteria. Sixty-five questionnaires were administered to specialised physicians. Both patients and physicians perceived the IBD-related QoC as being satisfactory. Furthermore, this study revealed areas of shortcomings where it comes to patient perceptions. Female sex and the presence of negatively impacting disease characteristics (presence of significant pain or discomfort, lack of energy, feeling fatigued most of the time, experiencing anxiety or depression in the last 2 weeks) were associated with lower satisfaction levels.ConclusionsOur findings can be used in establishing strategies aimed at improving patient QoC and defining strategic priorities. These data can aid in improving the communication of the pressing needs of IBD patients, to both the public payers and health authorities.

Abstract Background and aim Data on the radiologic evaluation of perianal fistulizing Crohn’s disease (PFCD) naïve to anti-tumor necrosis factor therapy are scarce, especially in Asian populations. We assessed the effectiveness of infliximab (IFX) on PFCD and explored predictors of ‘deep remission’ based on clinical and radiologic assessments. Methods Patients with Crohn’s disease and active anal fistulas attending our care center for IFX therapy were prospectively enrolled. Each patient underwent clinical examination according to the Fistula Drainage Assessment Index, endoscopy for assessment of Crohn’s Disease Activity Index (CDAI) and Perianal Crohn’s Disease Activity Index (PCDAI), magnetic resonance imaging (MRI) to determine Van Assche score and Ng score, and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy (Week 32). Results Among 38 patients treated with IFX, 52.6% achieved clinical remission based on the Fistula Drainage Assessment Index and 42.1% achieved deep remission based on Ng score. Van Assche score (from 14.5 ± 4.26 to 7.36 ± 7.53), CDAI (from 170 ± 92 to 71 ± 69) and PCDAI (from 7.45 ± 2.65 to 2.44 ± 3.20) decreased significantly after six IFX treatments. The only predictor of deep remission was simple fistula (P = 0.004, odds ratio = 3.802, 95% confidence interval: 1.541–9.383). Conclusions IFX has been shown to have appreciable effectiveness in Chinese patients with PFCD. MRI is the gold standard for evaluating PFCD, but Van Assche score has some limitations.

Perianal fistulizing Crohn's disease (pfCD)often indicates aggressive and refractory phenotype. Two-thirds of the patients with pfCD will relapse,so the treatment is really challenging. Currently,biological agents have made great progress. The application of biological agents such as infliximab brings new hope to the treatment of pfCD. This article reviewed the application of biological agents in treatment of pfCD.

Background Data on the radiologic evaluation of perianal fistulizing Crohn’s disease (PFCD) naive to anti-tumour necrosis factor therapy are scarce, especially in Asian populations. We assessed the effectiveness of infliximab (IFX) and azathioprine on PFCD and explored predictors of ‘deep remission’ based on clinical and radiologic assessments. Methods Patients with Crohn’s disease and active anal fistulas attending our centre for IFX therapy were prospectively enrolled. Each patient underwent clinical examination according to the Fistula Drainage Assessment Index, magnetic resonance imaging (MRI) to determine Van Assche score, Ng score, and main fistula length, endoscopy, assessment of Crohn’s disease activity index (CDAI) and perianal Crohn’s disease activity index (PCDAI), and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy (Week 32). Patients with PFCD treated with other medicines such as FK 506 or mesalazine and evaluated by two MRIs were retrospectively enrolled. Results Of 38 patients treated with IFX, 52.6% achieved clinical remission, and 42.1% achieved deep remission. The only predictor of deep remission was simple fistula (p=0.004, odds ratio=3.802, 95% confidence interval: 1.541–9.383). Van Assche score (from 14.5±4.26 to 7.36±7.53; figure 1), CDAI (from 170±92 to 71±69), and PCDAI (from 7.45±2.65 to 2.44±3.2) decreased significantly after six IFX treatments. Our findings suggest that Van Assche score has some limitations related to its inability to reflect new fistulas and abscesses in some circumstances. We used Ng score to compare the changes between the initial and follow-up MRIs in each patient, which is more objective and suitable for monitoring the therapeutic effect. Conclusions IFX is effective for the treatment of PFCD. MRI is the gold standard for evaluating PFCD, but Van Assche score has some limitations.