Background:The impact of probiotics on non-Helicobacter pylori gastric microbiota and its role in microbial restoration after eradication were relatively unknown. We aimed to explore the effect of H. pylori eradication and probiotic intervention on gastric microbiota in young adults.Methods: Fifty-six H. pylori-negative and 95 H. pylori-positive subjects aged 19-30 were included in this study. H. pylori-infected individuals were randomly assigned to quadruple therapy, probiotics supplemented quadruple therapy, or probiotics monotherapy group. Gastric mucosa and gastric juice samples were collected before and 2 months after treatment for 16SrRNA gene sequencing. Results:The gastric microbial community structure and composition differed from H. pylori-negative subjects 2 months after successful H. pylori eradication. The α diversity of gastric mucosal microbiota significantly increased and was higher than H. pylorinegative subjects, while the α diversity of gastric juice microbiota decreased and was lower than the H. pylori-negative. After probiotics supplemented eradication treatment, Bifidobacterium was enriched in gastric mucosa, Lactobacillus was enriched in gastric juice, potentially pathogenic bacteria such as Fusobacterium and Campylobacter decreased, and the microbial diversity was closer to that of H. pylori-negative subjects compared to quadruple therapy group. Probiotics monotherapy significantly altered the diversity, community structure, and composition of gastric microbiota but showed no advantage in H. pylori inhibition and upregulating beneficial bacteria such as Bifidobacterium and Lactobacillus and related metabolism pathways. Certain potentially pathogenic bacteria such as Fusobacterium increased after probiotic monotherapy. Conclusion:H. pylori eradication significantly disrupted gastric microbiota in young adults and could not be restored in a short time. Probiotics supplementation partially helped restore the gastric dysbiosis caused by eradication therapy, but it might be unnecessary for H. pylori-infected young adults to take probiotics alone.

Background: Proline levels are significantly increased in tumor specimens and urine samples from gastric cancer (GC) patients, and we previously showed that intracellular proline levels significantly differ between human GC cell lines and normal gastric epithelial cells. Pyrroline-5-carboxylate reductase 1 (PYCR1) is the key enzyme in intracellular proline synthesis, but its role in GC remains largely unknown.Methods: Bioinformatic analysis and immunohistochemical (IHC) staining with a tissue microarray were conducted to assess the association between PYCR1 expression and clinical parameters. PYCR1 downregulation and overexpression were then established in two GC cell lines (AGS and MKN28 cells) to determine whether PYCR1 promotes malignant behavior in GC. Gene set enrichment analysis (GSEA) was further performed to investigate the pathway regulating PYCR1 in GC.Results: PYCR1 expression was up-regulated in different GC cohorts. High PYCR1 protein expression was correlated with advanced tumor stage, aggressive histological type and high Ki-67 index. High PYCR1 expression in GC tissues was an indicator of poor outcome in GC patients. In vitro, PYCR1 knockdown markedly attenuated GC cells growth and promoted apoptosis, while overexpression produced the opposite effects. GSEA analysis indicated PI3K/Akt axis was strongly correlated with PYCR1 expression and that PIK3CB and AKT1 mRNA expression was positively associated with PYCR1 in GC tissues. PI3K inhibition further significantly reduced PYCR1 mRNA and protein expression. Moreover, as PYCR1 is a mitochondrial endomembrane protein, nutrient stress induced by glucose deprivation also regulated PYCR1 expression.Conclusions: PYCR1 is highly expressed in GC and acts as a mitochondrial oncogene to induce cancer progression by enhancing tumor proliferation and responding to metabolic stress. PYCR1 is a novel prognostic marker and a potential therapeutic target in GC.

Objective: Peroral endoscopic myotomy (POEM) is an emerging endoscopic treatment for achalasia and the long-term efficacy of POEM remains to be evaluated. This study compared the outcomes of POEM with that of the standard laparoscopic Heller myotomy (LHM) for achalasia. Materials and Methods: Achalasia patients treated by POEM or LHM were retrospectively analyzed, with a minimum postoperative follow-up of 3 years. Perioperative outcomes and long-term outcomes including treatment success (Eckardt score ≤3), occurrence of gastroesophageal reflux disease (GERD) (GerdQ score ≥9) and quality of life (36-item short form) were compared. Results: Thirteen patients who underwent POEM were compared with 18 patients who received LHM. These patients were similar in age, sex, symptoms duration, Eckardt score, and previous therapy (all P>0.05). Mean myotomy lengths were similar (P=0.73). Operation time was shorter in the POEM group (P=0.001). One patient (7.7%) developed pneumothorax after POEM and 1 patient (5.6%) experienced postoperative infection after LHM (P=1.00). Treatment success was achieved in 83.3% (9/12) of POEM patients and 80.0% (12/15) of LHM patients (P=1.00). Both POEM and LHM significantly reduced Eckardt score (both P=0.00). GERD rate was similar (8.3% vs. 6.7%, P=1.00). There was no difference in all aspects of quality of life between the 2 groups. Conclusions: Long-term outcomes indicate that POEM is an effective treatment that is comparable with LHM. More data of randomized trials comparing POEM with LHM will enrich the existing evidence.

The present study provides evidence that Slit2/Robo2 signaling mediates the pathogenesis of hepatic fibrogenesis and regulates HSCs biology, thus providing potential markers for HSCs, and therapeutic and diagnostic target toward liver fibrosis.