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Purpose: The majority of gastric cancer patients are diagnosed with late-stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early-stage gastric cancer (EGC) because the molecular events promoting gastric cancer initiation remain ill-defined.Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple data sets and independent gastric cancer patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer cells genetically engineered for suppressed activation of the oncogenic latent transcription factor STAT3. Human gastric cancer cells with modulated expression of the miR-200 family member miR-429 were also assessed for their proliferative response.Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited contrasting pro- and antiproliferative responses in human gastric cancer cells depending on their cellular histologic subtype. We also identified a miR-200 family–regulated 15-gene signature that integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology, and stage, and provides superior predictive power for overall survival compared with each EGC indicator alone.Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family–associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459–72. ©2018 AACR.

These figures and tables contain supporting (and essential) data to confirm the clinical utility of the miR-200 family and signature in early gastric cancer, as well as its regulation by STAT3. Supplementary Figure S1. The association of WHO intestinal-type GC sub-classes and individual TNM stage with the expression of miR-200 family members and miR-21 in TCGA GC patients. Supplementary Figure S2. The association between patient survival and expression of miR- 200s and a complete network map of GSEA results generated from TCGA GC patients. Supplementary Figure S3. miR-429 promotes AGS cells proliferation and clonigenicity. Supplementary Figure S4. The association between patient survival and expression of individual genes from the miR-200 family-associated 15-gene signature. Supplementary Figure S5. STAT3 activation correlates with miR-429 and other miR-200 members in mouse and human gastric epithelial cells. Supplementary Figure S6. Generation of STAT3 knockout human GC lines, and STAT3- independent transcriptional regulation of miR-200 family members. Supplementary Table S1. Clinicopathological features and demographics of GC patients from TCGA cohort used for expression profiling of hsa-miR-429. Supplementary Table S2. Chi-square analysis between the miR-200 family 15-gene signature and conventional key prognostic factors using two independent cohorts. 2 Supplementary Table S3. Multivariate analysis of overall survival comparing the miR-200 family 15-gene signature and other conventional clinical parameters including histology and tumor grade (differentiation) using updated TCGA data.

Background Jiuqu are vital saccharifying and fermenting agents for Chinese fermented foods. Natural ventilation during Jiuqu fermentation causes changes in temperature, oxygen and moisture content, resulting in mass and heat gradients from the outer to inner areas of Jiuqu blocks. In the present study, microbiota stratification in Jiuqu was investigated by single molecule real-time sequencing and culture isolation. The contributors of Bacillus to amylase activity of Jiuqu and the dynamics of their biomass during Jiuqu fermentation were also analyzed. Results The dominant orders, genera and species between the inner and outer layers of Huangjiu qu (HJQ) were similar, although they displayed greater variance in two layers of Baijiu qu (BJQ). Bacillus possessed the highest diversity (including 27 species) in Jiuqu. Bacillus licheniformis, Bacillus altitudinis, Bacillus subtilis, Bacillus amyloliquefaciens and Bacillus megaterium were most prevalent in HJQ, whereas B. licheniformis, B. amyloliquefaciens and Bacillus cereus were dominant in BJQ. Isolates of B. amyloliquefaciens, B. subtilis and B. cereus exhibited high activities of amylase and glucoamylase. Quantification of Bacillus members possessing genes of α-amylase revealed that B. cereus and B. licheniformis were the most dominant microbes to secret α-amylase in Jiuqu and their biomass were increasing during Jiuqu fermentation. Conclusion The present study demonstrates the microbial distribution in different layers of Jiuqu and clarifies the Bacillus species processing the activity of α-amylase. These results will help industries control the quality of Jiuqu by rationally selecting starters and optimizing their microbiota. © 2020 Society of Chemical Industry.

Purpose: The majority of gastric cancer patients are diagnosed with late-stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early-stage gastric cancer (EGC) because the molecular events promoting gastric cancer initiation remain ill-defined. Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple data sets and independent gastric cancer patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer cells genetically engineered for suppressed activation of the oncogenic latent transcription factor STAT3. Human gastric cancer cells with modulated expression of the miR-200 family member miR-429 were also assessed for their proliferative response. Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited contrasting pro- and antiproliferative responses in human gastric cancer cells depending on their cellular histologic subtype. We also identified a miR-200 family–regulated 15-gene signature that integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology, and stage, and provides superior predictive power for overall survival compared with each EGC indicator alone. Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family–associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459–72. ©2018 AACR.

This study aimed to investigate the molecular mechanism of systemic vasculitis via bioinformatics analysis. Gene express profile of E-GEOD-16945 (13 Takayasu arteritis samples and 13 control samples) was downloaded from European Bioinformatics Institute (EBI) database. Differentially expressed genes (DEGs) were screened between Takayasu arteritis and normal controls (|log FC| > 1). Basic local alignment search tool (BLASTX) was used for the Clusters of Orthologous Groups (COG) classification of DEGs. Gene ontology analysis was performed for the DEGs (P < 0.05). A gene expression network was built with DEGs. Mcode in Cytoscape software was used to extract modules from the network (degree ≥ 2, K-core ≥ 2 and adjusted P-value < 0.05) followed by pathway analysis using GenMAPP (false discovery rate < 0.05). A total of 747 DEGs were identified. There were 16 significant GO function terms enriched with DEGs, of which immune and defence response was the most significant GO term. Totally, three modules were extracted from gene expression network, including one module constituted with upregulated genes and two modules constituted with downregulated genes. Furthermore, human leucocyte antigen (HLA)-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA in the downregulated modules were significantly linked to immune-related pathways (intestinal immune network for IgA production and systemic lupus erythematosus pathways), while ribosomal protein L 31 (RPL31), RPS3A and RPL9 in the upregulated module were enriched in ribosome pathway. The immune-related pathways, ribosome pathway, immune-related genes including (HLA-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA) and ribosome-related genes (RPL31, RPS3A and RPL9) might be involved in systemic vasculitis.

Conventional high ligation and stripping of the great saphenous vein (GSV) has a good curative effect but is highly traumatic with a considerable relapse rate. Subfascial endoscopic perforator surgery (SEPS) plus endovenous laser treatment (EVLT) could be applied as individual therapy. This study aimed to evaluate the feasibility of performing combined SEPS and EVLT without impacting GSV in the management of valvular insufficiency of the lower-limb venous perforators.Placement of lower-limb venous perforator insufficiency was marked by ascending phlebography in 83 affected limbs from September 2010 to June 2011. After randomization, SEPS was performed on 41 limbs to address the insufficiency of the venous perforators under the deep fascia, in combination with EVLT to close the superficial varicose veins without impacting the GSV. The remaining 42 limbs were treated using traditional GSV phlebectomy as controls.Postoperatively, all varicose veins were resolved, with lightening of the pigmentation and healing of the ulcer. Within a follow-up period of 5 - 11 months, no symptoms had recurred. Compared with the control group, the operation time, the number of incisions sutured, and the in-hospital time decreased on average by 1.5 hours, 4.7, and 6.8 days, respectively (P0.01 in all cases).Combined SEPS and EVLT for treatment of valvular insufficiency of the lower-limb venous perforators offer the advantages of microtrauma and rapid cure.