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To clarify the endoscopic, clinicopathological, and growth characteristics of minute gastric cancer (MGC) and to improve its detection rate.Patients with early gastric cancer who underwent endoscopic submucosal dissection from July 2012 to September 2021 were retrospectively reviewed. MGC was defined as gastric cancer of 5 mm or less in size. Preoperative and postoperative endoscopic and pathological data were collected and analyzed. Follow-up information was collected until 9 April 2022.Eighty patients were enrolled, with 82 lesions observed under endoscopy and 87 diagnosed histopathologically. All patients received en bloc and curative resection. Compared with the time point when the last endoscopic examiniation prior to lesion deteciton was performed (t0), 64.29% of patients with MGC had disease progression at lesion detection (t1). However, 21.43% showed normal or only atrophic changes under white-light endoscopy, and their lesions were diagnosed accidentally by random biopsy. The majority of MGC lesions presented as type IIc and reddish, and 95.00% of cases had well-differentiated tubular adenocarcinoma. The mean growth rate of MGC was 0.0071 mm/day, and it took an average of 3.42 years to grow to 5 mm. There was no significant difference in the depth of invasion between the low cellular atypia group and the high cellular atypia group.Type IIc and reddish appearance are main endoscopic features of MGC. For cases with no obvious endoscopic changes, multipoint biopsy is helpful. MGC is mostly well differentiated and grows relatively slowly; therefore, MGC can still have a chance to be identified and resected curatively if it is missed diagnosed.

Aim Emperipolesis, the cell-in-cell structure, is one of the pathological diagnostic standard of AIH. We have already identified that CD8+ T cells participated in the emperipolesis process in liver tissue of AIH patients. In this study, we aimed to clarify the characteristics and molecular mechanisms of emperipolesis in the patients with AIH in vitro and in mice with α-GalCer-induced acute hepatitis. Methods Peripheral blood mononuclear cell (PBMC) of patients with variant chronic liver diseases and healthy controls were co-cultured with hepatic cell line to induce emperipolesis in vitro. Confocal staining was performed to illustrate the cellular types and potential mechanisms of emperipolesis in AIH. In addition, the mouse model of α-GalCer-induced acute hepatitis which mimics human AIH in several features, was used to confirm the role of CD44/p-ERM/F-actin in the emperipolesis process in vivo. Results In co-culture system with PBMC and hepatic cell line, emperipolesis was observed most common in the patients with AIH. CD8+ T cells were the major cells participated in the emperipolesis process, and penetrated into hepatocytes actively via CD44/p-ERM/F-actin pathway. As a result, most CD8+ T cells engulfed in hepatocytes undergo self-apoptosis. In α-GalCer-induced acute hepatitis model, emperipolesis was observed around the inflammatory foci, and was inhibited by Ezrin phosphorylation inhibitor NSC668394. Similarly, activated murine CD8+ T cells penetrated into primary hepatocytes via CD44/p-ERM/F-actin pathway in vitro. Conclusions CD8+ T cells penetrated into hepatocytes actively via CD44/p-ERM/F-actin signaling pathway and undergo apoptosis, may be a compensative mechanism to attenuate overwhelming immune attack in AIH. This article is protected by copyright. All rights reserved.

To conduct a sub-cohort analysis to evaluate the efficacy and safety of linaclotide in Chinese patients with constipation-predominant irritable bowel syndrome (IBS-C) using data from a completed trial (NCT01880424).In this phase III, double-blind, placebo-controlled trial, IBS-C patients were randomized to receive linaclotide (290 μg/d) or placebo for 12 weeks. Efficacy was assessed with two co-primary responder end-points (12-wk abdominal pain/discomfort: ≥30% reduction in either score with neither deteriorating from baseline for ≥6 wks; 12-wk IBS degree of relief: score ≤2 for ≥ 6 wks), seven secondary endpoints and several additional end-points.In total, 659 Chinese IBS-C patients received linaclotide (n = 327) or placebo (n = 332). The 12-week abdominal pain/discomfort end-point was met in 62.1% and 53.3% of the linaclotide-treated and placebo-treated patients, respectively (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05-1.96, P = 0.023); the 12-week IBS degree of relief end-point was achieved in 32.7% and 16.9% of the patients treated with linaclotide and placebo, respectively (OR 2.40, 95% CI 1.66-3.47, P 0.001). The linaclotide-treated patients had a shorter time to the first spontaneous bowel movement than the placebo-treated patients (23.6 h vs 43.7 h, P 0.001). Linaclotide produced significantly greater improvement than placebo in all secondary end-points from the first 2 weeks (all P 0.001). Diarrhea was reported in 8.3% of linaclotide-treated patients and 1.2% of placebo-treated patients.Linaclotide (290 μg/d) was efficacious and well-tolerated in Chinese IBS-C patients with a rapid onset of effect.

Objectives The histone methylation and acetylation pathway genes regulate cell growth and survival. Aberrations in this pathway are implicated in a variety of cancers. This study aimed to identify germline genetic variants in histone methylation and acetylation pathway genes that may contribute to risk in eight types of cancers and to explore the relation between the whole pathway and their risks in these types of cancers. Methods Germline genetic variants in 89 genes in the histone methylation and acetylation pathway were explored. Gene-based and pathway-based associations with eight types of cancers were analyzed using logistic regression models and the permutation-based adaptive rank-truncated product method, respectively. Results Gene-level associations revealed that genetic variants in 45 genes were significantly associated with the risk of cancer. The total histone methylation and acetylation pathway was significantly associated with the risk of esophageal squamous cell carcinoma (P = 0.0492) and prostate (P = 0.0038), lung (P = 0.00015), and bladder cancer (P = 0.00135), but not with breast (P = 0.182), pancreatic (P = 0.336) and gastric cancer (P = 0.347) and renal cell carcinoma (P =0.828). Conclusions Our study suggested there is an association between germline genetic variation at the overall histone methylation and acetylation pathway level and some individual genes with cancer risk. Further studies are needed to validate these relations and to explore relative mechanisms.

Programmed death-ligand 1 (PD-L1) expression in colorectal cancers (CRCs) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, therapeutic response has also been found in patients without PD-L1 expression in the primary tumor. Here we show that PD-L1 expression is significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD-L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD-L1 was found in 81.8% metastatic CRCs, being significantly more prevalent than in primary CRCs (40.9%; P = 0.012, Fisher's exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD-L1 expression frequently increased during the metastatic process. However, PD-L1 expression is rarely decreased in metastatic lesion. Intratumoral heterogeneity expression of PD-L1 was found in both metastatic CRCs (28.6%) and primary CRCs (33.3%). In conclusion, PD-L1 is prevalently expressed in metastatic CRCs, and increased PD-L1 expression is frequently found in metastatic CRC as compared to primary tumor. These findings suggest that PD-L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy.

Aim To assess efficacy ofDA alginate-antacidchewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD) Methods Forty-fourpatients reporting moderately severe heartburn symptomsunderwent two pHmonitoring visits. Treatment sequence was randomized:patients receivedDAalginate-antacid or placebo at one visit and the alternate treatment seven days later. Aftera standardizedreflux-provoking meal,patients took four tablets of DAalginate-antacid or placebo. Esophageal pH was measured for 4 h post-dosing,using an electrode positioned 5 cm above the lower esophageal sphincter.Primary endpoint: percentage of 4-hpost-dosing period with pH

Objectives Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. Methods Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. Results Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. Conclusion The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.

The scarcity of donor livers and the impracticality of hepatocyte transplantation represent the biggest obstacles for the treatment of liver failure. Adipose-derived stem cells, with their ability to differentiate into the hepatic lineage, provide a reliable alternative cell source with clear ethical and practical advantages. Moreover, adipose-derived stem cells can effectively repair liver damage by the dominant indirect pattern and increase the number of hepatocytes by the secondary direct pattern. In recent years, the development of the indirect pattern, which mainly includes immunomodulatory and trophic effects, has become a hot topic in the field of cell engineering. Therefore, adipose-derived stem cells are considered to be ideal therapeutic stem cells for human liver regeneration. In this article, we reviewed the advantages of adipose-derived stem cells in liver regeneration, and explore their underlying mechanisms.

Up to 100 trillion bacteria are harbored in the human intestine with a mutualistic and interdependent relationship with the host during a long period of co-evolution. The so-called intestinal microbiota (IM) fulfill important metabolic tasks and the impaired stability may lead to IM-related diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), metabolic syndrome (MS), liver diseases, and so on. Here, we review the past and development of IM research in China, including the achievements that Chinese researchers have made both in basic and clinical scientific field. Moreover, we evaluate the contributions of the National Natural Science Foundation of China (NSFC), the 973 National Basic Research Program of China (973 Program), the 863 National High Technology Research and Development Program of China (863 Program), and funds from the public health industry in the field of IM research.

Objectives Confocal laser endomicroscopy (CLE) consists of endoscope-based CLE (eCLE) and probe-based CLE (pCLE). This study aimed to compare eCLE and pCLE in their diagnostic yield in different parts of the gastrointestinal (GI) tract. Methods Consecutive patients were scheduled for CLE examination due to GI symptoms. All patients were randomly assigned to eCLE or pCLE group and underwent a programmed procedure using one type of CLE. Differences in procedure time, complication rate, CLE image quality and image acquisition feasibility between these two types of CLE for esophagogastroduodenoscopy (EGD) and colonoscopy were calculated. Results Altogether 513 CLE procedures were performed, including 324 EGD and 189 colonoscopy. The procedure time of pCLE was significantly shorter than that of eCLE both in EGD and colonoscopy (16.78 min vs 18.13 min for EGD, P = 0.027; 32.48 min vs 39.89 min for colonoscopy, P

Programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, therapeutic response has also been found in patients without PD-L1 expression in the primary tumor. In the present study, we aimed to clarify the prevalence of PD-L1 in primary and metastatic CRC.The expression of PD-L1 was determined by immunohistochemistry in matched primary and metastatic CRC.PD-L1 expression was significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD-L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD-L1 was found in 81.8% of metastatic CRC, being significantly more prevalent than in primary CRC (40.9%; P = 0.012, Fisher's exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD-L1 expression frequently increased during the metastatic process. However, PD-L1 expression was rarely decreased in metastatic lesions. Intratumoral heterogeneity expression of PD-L1 was found in both metastatic CRC (22.2%) and primary CRCs (33.3%). PD-L1 was prevalently expressed in metastatic CRC, and increased PD-L1 expression was frequently found in metastatic CRC as compared to primary tumors.PD-L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy.

The histone methylation and acetylation pathway genes regulate cell growth and survival. Aberrations in this pathway are implicated in a variety of cancers. This study aimed to identify germline genetic variants in histone methylation and acetylation pathway genes that may contribute to risk in eight types of cancers and to explore the relation between the whole pathway and their risks in these types of cancers.Germline genetic variants in 89 genes in the histone methylation and acetylation pathway were explored. Gene-based and pathway-based associations with eight types of cancers were analyzed using logistic regression models and the permutation-based adaptive rank-truncated product method, respectively.Gene-level associations revealed that genetic variants in 45 genes were significantly associated with the risk of cancer. The total histone methylation and acetylation pathway was significantly associated with the risk of esophageal squamous cell carcinoma (P = 0.0492) and prostate (P = 0.0038), lung (P = 0.00015), and bladder cancer (P = 0.00135), but not with breast (P = 0.182), pancreatic (P = 0.336) and gastric cancer (P = 0.347) and renal cell carcinoma (P =0.828).Our study suggested there is an association between germline genetic variation at the overall histone methylation and acetylation pathway level and some individual genes with cancer risk. Further studies are needed to validate these relations and to explore relative mechanisms.

Objective To investigate the molecular mechanism of colorectal cancer (CRC) cell apoptosis induced by the Jumonji domain containing 2B (JMJD2B) silencing. Methods Both HCT116 and LoVo CRC cell lines were used for analyses. Cell apoptosis after JMJD2B silencing was determined by flow cytometry. JC-1 fluorescence probe was applied to measure the mitochondrial outer membrane permeabilization by flow cytometry and fluorescence microscopy. Immunofluorescence was used to detect cytochrome C translocation from mitochondria to cytosol after JMJD2B silencing. The efficacy of JMJD2B silencing on the protein levels of Bcl-2 family, caspase proteins, CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were detected by Western blot. Results JMJD2B silencing induced CRC cell apoptosis via a decrease of the anti-apoptotic gene Bcl-2 family expression, leading to the translocation of Bak and Bax proteins and the promotion of mitochondrial membrane disruption, resulting in the release of cytochrome C from mitochondria and subsequent caspase-9 and caspase-3 cleavage. It also increased the amount of cleaved caspase-8 involved in the death receptor-related apoptotic pathway. Bcl-2 homology 3 interacting-domain death agonist (Bid), a specific caspase-8 substrate involved in the Fas signaling pathway, subsequently induced cleavage via caspase-8 activation. However, levels of CHOP and GRP78 remained unchanged after JMJD2B silencing. Conclusions JMJD2B silencing induced CRC cell apoptosis via both mitochondria-related and death receptor-related pathways. The cleavage of Bid activated by caspase-8 might serve as a crosstalk mediator between these two pathways in CRC.

Gastric cancer (GC) is one of the most common cancers in the world. The incidence and mortality rate of GC vary among different countries. It is suggested that GC is the result of the interaction between Helicobacter pylori (H. pylori) infection and the genetic and environmental factors in the host. H. pylori infection is the trigger of intestinal gastric adenocarcinoma. The incidence of GC is highest in East Asia and East Europe, but much lower in Africa; however, H. pylori infection is commonly seen in Africa, which is known as the African enigma. The 5-year survival of early GC is far better than that of advanced GC. A high detection rate of early GC could help us to conquer GC. A decreasing trend of GC incidence has been witnessed worldwide. With the improvement of living conditions and the achievements of scientific research, it seems possible that there will be a further reduction in the incidence of GC in the new century.

To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD).Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH4. Secondary end-points were number of acid reflux episodes (pH4), longest reflux time and DeMeester scores.All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs.DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms.

OBJECTIVE: The best cure for colorectal cancer (CRC) lies on its early diagnosis and treatment. We aimed to provide the epidemiological features of advanced colorectal adenoma (A-CRA) and CRC in symptomatic patients and to determine whether the incidences of A-CRA and CRC increased simultaneously in China between 1990 and 2009. METHODS: A total of 157 943 patients who had undergone a colonoscopy from 1990 to 2009 were enrolled, of which 6 777 patients had A-CRA and 3 503 had CRC. They were compared with controls in a stratified analysis. The detection rates of A-CRA and CRC in the 1990s and 2000s were also compared. RESULTS: The detection rate of A-CRA increased 1.88-fold over the two decades, while that of CRC increased 0.66-fold. The percentages of patients with A-CRA and CRC who were elder than 50 years were significantly higher in the 2000s than those in the 1990s (P = 0.000). The changes of location of A-CRA and CRC during the two decades indicated a shift of lesions from the distal colon to proximal colon. CONCLUSION: There was a significant increase in detection rate of A-CRA in the 2000s, but CRC did not increase at a similar speed. Our results indicated that the early detection and removal of colorectal adenoma in symptomatic patients might decrease the incidence of CRC.