Unravelling diagnostic clusters and immune landscapes of disulfidptosis patterns in gastric cancer through bioinformatic assay.

Disulfidptosis is a novel type of cell death mediated by SLC7A11-induced disulfide stress. Gastric cancer (GC) is a common malignant gastrointestinal tumor. Existing evidence shows that SLC7A11 can regulate cell death and improve the progression of GC, suggesting disulfidptosis may exist in the pathological process of GC. However, the underlying functions of disulfidptosis regulators in GC remain unknown. The dataset of GSE54129 was screened to comprehensively investigate the disulfidptosis-related diagnostic clusters and immune landscapes in GC. Totally 15 significant disulfidptosis regulators were identified via difference analysis between GC samples and controls. Then random forest model was utilized to assess their importance score (mean decrease Gini). Then a nomogram model was constructed, which could offer benefit to patients based on our subsequent decision curve analysis. All the included GC patients were divided into 2 disulfidptosis subgroups (clusterA and clusterB) according to the significant disulfidptosis regulators in virtue of consensus clustering analysis. The disulfidptosis score of each sample was calculated through PCA algorithms to quantify the disulfidptosis subtypes. Patients from clusterB exhibited lower disulfidptosis scores than those of patients in clusterA. In addition, we found that the cases in clusterB were closely associated with the immunity of activated CD4 T cell, etc., while clusterA was linked to immature dendritic cell, mast cell, natural killer T cell, natural killer cell, etc., which has a higher disulfidptosis score. Therefore, disulfidptosis regulators play an important role in the pathological process of GC, providing a promising marker and an immunotherapeutic strategy for future GC therapy.

[Clinical experience and academic thoughts of Professor LIU Feng-bin on case series of gastroesophageal reflux disease based on data mining].

To analyze and summarize Professor LIU Feng-bin's clinical experience and academic thoughts on gastroesophageal reflux disease (GERD), the study group adopted the retrospective study for case series and expert interview, extracted the retrospective data, including the herbs, diseases, syndrome type, medical expense and quantity of herbs of GERD patients attended the First Affiliated Hospital of Guangzhou University of Chinese Medicine. Statistical description and binary Logistic regression were used for the identification and modification of syndrome type and initial core herbs. After expert interviews were performed for the syndrome type and herbs, the final scheme were formed. A total of 112 GERD patients ages（48.97±13.13）y; male: 35 (31.3%), female: 77(68.7%) were enrolled. The numbers of patients with liver and stomach incoordination syndrome, heat stagnation of liver and stomach syndrome, syndrome of dual deficiency of Qi and Yin, syndrome of spleen deficiency and dampness-heat, spleen-stomach disharmony syndrome were 40, 26, 19, 17 and 10, respectively. The patients used totally 80 herbs, and 26 of them had significant differences among different syndrome groups. According to the logistic regression analysis on the 23 herbs used by 112 patients, the herbs scheme was modified for the second time. After the expert interviews and modification, the final consensus was reached. The main causes for GERD were dietary irregularities, moodiness, and weak constitution. The basic mechanism of GERD was spleen deficiency with Qi adverseness. The spleen-stomach disharmony syndrome was deleted by expert interviews. The 10 core herbs for GERD treatment were Taizishen(Pseudostellariae Radix), Fuling(Poria), Baizhu(Atractylodismacrocephalae Rhizoma), Gancao(Glycyrrhizae Radix Et Rhizoma), Zhebeimu(Fritillariae Thunbergii Bulbus), Haipiaoxiao(Sepiae Endoconcha), Zhiqiao(Aurantii Fructus), Chenxiang(Alosewood), Pugongying(Taraxaci Herba), Zhizitan(Cape Jasmine Fruit). The modification and psychological and diet interventions were also identified. This study summarized Professor LIU Feng-bin's clinical experience and academic thoughts of chronic atrophic gastritis based on data mining of case series and expert interviews. The quality of methodologies and report were both well. The results provide a foundation and ideas for further study on the complex intervention for GERD, and can be directly applied in clinical practice.

Interpreting the Chinese version of quality of life questionnaire for functional digestive disorders.

BACKGROUND AND AIM: The Chinese version quality of life questionnaire for functional digestive disorders (Chin-FDDQL) is a useful health assessment instrument for functional dyspepsia. This study aims to identify its score interpretation for clinical practice. METHODS: Data of Chin-FDDQL from the functional dyspepsia patients (≥ 18 years) between November 2009 and April 2013 were enrolled in the 1st and 14th day. After baseline and responsiveness analysis, the single score interpretation and percentile ranks were established. The statistically reliable change was defined with effect size, standardized response mean, minimal detectable change, and others. Then the receiver operating characteristic curve analysis for health improvement was performed to define the clinically important change. RESULTS: Two hundred two functional dyspepsia patients, 150 healthy participants, and 25 missing data were enrolled for analysis. Compared with the intake patients, the discharged and healthy persons have significant better health status in all domains (P < 0.001, expect discomfort in discharged people, P = 0.142), totally contrast to missing data. The reliability for single total intake and discharge were both ± 1. Based on score distribution, the 25th, 50th, and 75th percentile ranks were 49, 58, and 66 for intake scores and 59, 65, and 72 for discharge scores, respectively. The minimal detectable change and Reliable Change Index were 6 and 11 for total score. Receiver operating characteristic analyses supported that total score changes 4 or more represented minimal clinically important improvement. CONCLUSIONS: The score interpretation system of the Chin-FDDQL could assist clinician's decision making during the therapy practice.

miR-155 targets Est-1 and induces ulcerative colitis via the IL-23/17/6-mediated Th17 pathway.

BACKGROUND: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) affecting millions of people worldwide. miR-155 has been reported to be upregulated in various inflammatory diseases and is a positive regulator of the T-cell response. IL-17 secreting helper T (Th17) cells have been heavily implicated in tissue-specific immune pathology, including UC. METHODS AND RESULTS: Therefore, we targeted miR-155 and investigated its expression levels in a DSS-induced UC mouse model, revealing increased expression. Est-1 expression was found to have decreased, but the levels of IL-23/17/6 were raised significantly and Th17 had experienced an obvious increase. We overexpressed miR-155 using a lentiviral treatment. Increased miR-155 expression induced a more severe damage to colon tissues. In this case, the level of Est-1 decreased even further, thereby enhancing IL-23/17/6-mediated Th17 differentiation. CONCLUSION: miR-155 seems to target Est-1 and induces UC via the IL-23/17/6-mediated Th17 pathway.

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis.

BACKGROUND: Transforming growth factor-beta (TGF-ß) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-ß can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial. METHODS: The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-ß as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. RESULTS: Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-ß had a favourable impact on OS (HR = 1.68, 95% CI: 1.10-2.59) and DFS (HR = 1.11, 95% CI: 1.03-1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61-3.68) and 1.80 (95% CI: 1.33-2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61-3.31) and 1.11 (95% CI: 1.03-1.20), respectively. CONCLUSIONS: This meta-analysis demonstrates that TGF-ß can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.