The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults.

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. pylori-negative 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.

The study of methylation and single nucleotide polymorphisms of cancer-related genes in patients with early-stage ulcerative colitis.

Aim: To investigate the methylation status and single nucleotide polymorphisms (SNPs) of cancer-associated genes in ulcerative colitis (UC) patients and explore the potential mechanism for high cancer risk of UC. Methods: A total of 103 patients were enrolled in our study, which included 30 healthy subjects, 41 patients with early-stage UC, and 32 patients with colorectal cancer (CRC). Methylation status of cyclooxygenase 2 (COX2) and human RUNT-related transcription factor 3 (RUNX3) genes in colonic mucosa from 3 groups of subjects were detected by methylation-specific polymerase chain reaction (PCR). The SNPs TNF-α rs1800629 and IL-1 rs1143627 were genotyped by PCR and direct sequencing. Results: The methylation rate of RUNX3 gene within CRC group was 35.7%, which was significantly higher than the other two groups (Healthy control 5.9%, UC 15.4%, p = .040). There was no significant difference in the methylation rate of RUNX3 between early-stage UC group and healthy control group (p = .633). The methylation rate of COX2 gene, the genotypes (GG, AG) and alleles (A, G) of rs1800629, and the genotypes (CC,CT,TT) and alleles (C,T) of rs1143627 were not statistically different among three groups. Conclusion: In the early stage of UC, the methylation rate of cancer-related genes RUNX3 and COX2 and SNPs TNF-α rs1800629 and IL-1 rs1143627 were not significantly different compared with healthy subjects. The methylation rate of RUNX3 in CRC increased, while the methylation rate of COX2 and SNPs TNF-α rs1800629 and IL-1 rs1143627 did not change significantly compared with the other two groups.

Impact of media dependence: how emotional interactions between users and chat robots affect human socialization?

In the era of intelligent media, human users and chatbots have established a deep dependency relationship through communication, making media dependence a behavioral foundation that widely permeates human social practice. This article investigates how media dependence affects human social interaction during emotional interactions between human users and chatbots. Based on the theory of media dependence, the existing mature scales of media dependence and interpersonal communication were adapted, and 496 Replika user questionnaires were collected. After screening the validity of the questionnaires, 428 valid questionnaires were obtained. Descriptive statistical analysis, correlation analysis, multiple linear regression analysis, and mediation effect testing were used to analyze the impact of media dependence on human-computer emotional interaction. Results indicate a significant positive correlation between human-chatbot emotional interaction and human user social interaction. Media dependence significantly positively regulates emotional interactions between humans and chatbots. In addition, the social interactions of human users are partially influenced by factors such as user nature, age, education, and income.

Ring-Opening α,ß-Difunctionalization of Cyclopropanols with Azides Enables 4-Keto-Functionalized 1,2,3-Triazole Synthesis.

Selective C-C bond cleavage and transformation of organic small molecules to create products of increased value are one of the central goals in organic chemistry. In this study, we have developed a novel TEMPO-mediated ring-opening α,ß-difunctionalization of cyclopropyl alcohols with organic azides to prepare structurally important 4-keto-1,2,3-triazoles under metal- and additive-free conditions. This protocol not only provides a straightforward and efficient method for the synthesis of 4-keto-functionalized 1,2,3-triazoles in one pot but also accomplishes the goal of constructing α,ß-double C-N bonds via the ring opening of cyclopropyl alcohols for the first time. Additionally, the application of the skeletons of drugs and natural products and the synthesis of Kv1.5 channel blocker 4u further demonstrate the synthetic potential and practicability of this strategy.

Gastric duplication cysts: literature review and a case report of rare multiple gastric duplication cysts treated by endoscopic submucosal dissection.

Gastric duplication cysts (GDCs) are rare structural abnormalities, especially in adults. We first report a rare case of small multiple GDCs in a woman, which presents as a submucosal tumor (SMT) at the gastric antrum. In consideration of the patient's request for surgical treatment and minimally invasive resection, endoscopic submucosal dissection (ESD) was performed to remove the cyst. The case provides a reference for ESD surgery to remove small GDCs. So far, there is no consensus or practice guidelines for the diagnosis and management of GDCs. Herein we perform a comprehensive literature review and discussion on GDCs. GDCs are 'repetitive' cystic or tubular structures of gastric mucosa and muscularis mucosae, and share the muscularis propria and serous layer with the normal gastric wall. GDCs protruding into the stomach cavity can be diagnosed by endoscopic ultrasound (EUS), which has higher specificity and accuracy than CT and MRI. Some GDCs may cause complications, even cancerization. Therefore, we suggest that once found, the GDCs could be completely resected. For GDCs protruding into the stomach cavity, endoscopic surgery such as ESD can be adopted to remove the lesion. Endoscopic full-thickness resection (EFTR) may become an option for larger GDCs in the future. For extraluminal GDC, laparoscopic surgery is currently preferred. In this review, we summarized the structural and histopathological characteristics of GDCs and various treatment therapies, in order to provide experience and reference for the diagnosis and treatment of GDCs in the future.

Body Composition in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with body composition changes, which are associated with clinical prognosis, response to therapy, and quality of life in IBD patients. Therefore, it is critical to review the body composition distribution in IBD, summarize the potential factors affecting body composition distribution, and take steps to improve the body composition distribution of IBD patients as early as possible. In the current review, we searched PubMed via keywords 'inflammatory bowel disease', or 'IBD', or 'Crohn's disease', or 'CD', or 'ulcerative colitis', or 'UC', and 'body composition'. Malnutrition and sarcopenia are common in IBD patients and are associated with the clinical course, prognosis, and need for surgery. Disease activity, reduced nutrition intake, vitamin D deficiency, and intestinal dysbiosis are factors contributing to changed body composition. Early use of biological agents to induce remission is critical to improving body composition distribution in IBD patients, supplementation of vitamin D is also important, and moderate physical activity is recommended in IBD patients with clinical remission.

The construction of lattice-matched CdS-Ag2S heterojunction photocatalysts: High-intensity built-in electric field effectively boosts bulk-charge separation efficiency.

The built-in electric field of heterojunction can effectively promote carrier separation and transfer. While, its interface orientation is often random, leading to lattice mismatch and high resistance, thus limiting the efficiency of interfacial charge transfer. Herein, the lattice-matched heterojunction (CdS-Ag2S) was constructed by ion-exchange epitaxial growth. The results of surface photovoltage spectroscopy (SPV), transient photovoltage spectroscopy (TPV), and time-resolved photoluminescence (TRPL) show that the lattice-matched heterojunction has higher charge separation efficiency and longer photogenerated carrier lifetime than that of lattice-mismatched one. The lattice-matched CdS-Ag2S has a high built-in electric field (BIEF) value of 103.42 and a bulk-charge separation (BCS) efficiency of 68.71%, which is about three times higher than that of the lattice-mismatched heterojunction (CdS-Ag2S-M). In addition, the photodegradation efficiency of CdS-Ag2S towards norfloxacin (NOR) was also 3.4 times higher than that of CdS-Ag2S-M. The above results and density functional theory (DFT) calculations indicate that improving the lattice matching at the heterojunction is beneficial for establishing a high-intensity built-in electric field and effectively promoting bulk-charge separation efficiency, thus achieving excellent photocatalytic performance. This work provides an essential reference for the research of high-performance heterojunction photocatalysts.

Optimization, and biological evaluation of 3-O-ß-chacotriosyl betulinic acid amide derivatives as novel small-molecule Omicron.

SARS-CoV-2 Omicron viruses possess a high antigenic shift, and the approved anti-SARS-CoV-2 drugs are extremely limited, which makes the development of new antiviral drugs for the clinical treatment and prevention of SARS-CoV-2 outbreaks imperative. We have previously discovered a new series of markedly potent small-molecule inhibitors of SARS-CoV-2 virus entry, exampled by the hit compound 2. Here, we report a further study of bioisosteric replacement of the eater linker at the C-17 position of 2 with a variety of aromatic amine moieties, followed by a focused structure-activity relationship study, leading to the discovery of a series of novel 3-O-ß-chacotriosyl BA amide derivatives as small-molecule Omicron fusion inhibitors with improved potency and selectivity index. Particularly, our medicinal chemistry efforts have resulted in a potent, and efficacious lead compound S-10 with appreciable pharmacokinetic properties, which exhibited broad-spectrum potency against Omicron and other variants with EC50 values ranging from 0.82 to 5.45 µM. Mutagenesis studies confirmed that inhibition of Omicron viral entry was mediated by the direct interaction with S in the prefusion state. These results reveal that S-10 is suitable for further optimization as Omicron fusion inhibitors, with the potential to be developed as therapeutic agents for the treatment and control of SARS-CoV-2 ant its variants infections.

The necessity and appropriate range of the diagnostic "gray zone" of 13C-urea breath test.

Background: The 13C-urea breath test (13C-UBT) is preferred for non-invasive detection of Helicobacter pylori (H. pylori); however, its accuracy drops when results fall between 2‰ and 6‰ (called the gray zone). This study aimed to evaluate the accuracy of 13C-UBT (cut-off point 4‰) between 2‰ and 6‰, find a more appropriate gray zone, and identify the factors influencing 13C-UBT. Methods: Patients with 13C-UBT results 2‰-6‰, over an eight-year period, were studied. H. pylori infection was diagnosed if patients were positive for either Warthin-Starry staining or quantitative real-time polymerase chain reaction (real-time PCR), and excluded if both were negative. Accuracy of 13C-UBT under different cut-off points was calculated, and the factors affecting 13C-UBT were analyzed. Results: A total of 208 patients were included, of whom 129 were H. pylori-positive. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 13C-UBT were 71.32%, 83.54%, 64.08%, and 87.62%, respectively. When the cut-off point was changed to 2.15‰, the NPV of 13C-UBT reached a maximum (76.47%); when the cut-off point was changed to 4.95‰, PPV reached its maximum (93.22%). Therefore, the original gray zone (2‰-6‰) was adjusted to 2‰-4.95‰. Gastric antral intestinal metaplasia (OR = 3.055, 95% CI: 1.003-9.309) was an independent risk factor for false-negative 13C-UBT. Conclusions: Accuracy of 13C-UBT over 2‰-6‰ was poor, and the gray zone was changed to 2‰-4.95‰. 13C-UBT results over 2‰-4.95‰ should be interpreted with caution during mass screening of H. pylori, especially for patients with gastric antral intestinal metaplasia.

Status of Gene Methylation and Polymorphism in Different Courses of Ulcerative Colitis and Their Comparison with Sporadic Colorectal Cancer.

BACKGROUND: The objective of this study is to explore the common genetic and epigenetic mechanism of ulcerative colitis (UC) and sporadic colorectal cancer (SCRC) by observing genes methylation level and single nucleotide polymorphisms (SNPs) of different disease courses in UC and SCRC. METHODS: Two hundred subjects were enrolled, including 40 in the healthy control (HC) group, 50 in the short disease course UC group (SUC), 52 in the long disease course UC group (LUC), and 58 in the SCRC group. Methylation-specific polymerase chain reaction was used to detect the methylation of MINT1 and cyclooxygenase 2 (COX-2) gene. Single nucleotide polymorphisms of interleukin (IL)-23R rs10889677 and IL-1ß rs1143627 were detected by Sanger sequencing. RESULTS: Compared with HCs (32.5%), methylation level of MINT1 was significantly increased in SCRC (67.2%; P = 0.001) and was a risk factor for CRC (odds ratio, [OR] 4.26). The methylation ratios of COX-2 were 95.0%, 58.0%, 23.1%, and 24.1% in HC, SUC, LUC, and SCRC, respectively, which were negatively correlated with the disease course of UC (r = -0.290). Hypermethylation of COX-2 was a protective factor for SUC (OR, 0.11), LUC (OR, 0.02), and SCRC (OR, 0.03; P < 0.05). Compared with HCs, rs10889677 allele A was a risk factor for SUC and LUC, and rs1143627 allele T was a protective factor for SUC and LUC. Genotype TT was a protective factor for SUC. CONCLUSION: The hypomethylation of COX-2 gene was a common risk factor and epigenetic modification for UC and SCRC, which might be one of the mechanisms through which UC patients were susceptible to CRC. The hypermethylation of MINT1 was a risk factor for SCRC but not for UC; alleles of IL-23Rrs10889677 and IL-1ßrs1143627 were related to UC but not to SCRC.

Pyrroline-5-carboxylate reductase 1 (PYCR1) upregulation contributes to gastric cancer progression and indicates poor survival outcome.

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.

Serum amyloid A levels in patients with liver diseases.

BACKGROUND: Serum amyloid A (SAA) is an acute phase protein mainly synthesized by the liver. SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells, the major scar forming cells in the liver. However, few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases. AIM: To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B (CHB) patients. METHODS: Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study. The patients included 205 with CHB, 22 with active autoimmune liver disease (AILD), 21 with nonalcoholic steatohepatitis (NASH), 14 with drug-induced liver injury (DILI), and 16 with pyogenic liver abscess. Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level. Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls. Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error (alpha = 0.05/6 = 0.008). For statistical tests of other variables, P < 0.05 was considered statistically significant. Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis. RESULTS: All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients, with the highest SAA level found in patients with pyogenic liver abscess (398.4 ± 246.8 mg/L). Patients with active AILD (19.73 ± 24.81 mg/L) or DILI (8.036 ± 5.685 mg/L) showed higher SAA levels than those with active CHB (6.621 ± 6.776 mg/L) and NASH (6.624 ± 4.891 mg/L). Single (P < 0.001) and multivariate logistic regression analyses (P = 0.039) for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L. Serum levels of SAA and CRP (C-reactive protein) were positively correlated in patients with CHB (P < 0.001), pyogenic liver abscess (P = 0.045), and active AILD (P = 0.02). Serum levels of SAA (0.80-871.0 mg/L) had a broader fluctuation range than CRP (0.30-271.3 mg/L). CONCLUSION: Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess. It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.

Slit2-Robo2 signaling modulates the fibrogenic activity and migration of hepatic stellate cells.

BACKGROUND & AIM: Slit/Robo signaling was originally identified as a repulsive guidance cue in regulating axon branching and neuronal migration. Hepatic stellate cells (HSCs) are the key fibrogenic cells in the liver, which are migratory when activated, and express neural crest markers. The aim of the present study was to investigate the functional significance of Slit/Robo signaling in liver fibrogenesis and in HSCs. KEY FINDINGS: By transcriptomic analysis it was found that axon guidance signaling pathways were significantly upregulated in both diethylnitrosamine (DEN) and thioacetamide (TAA)-induced experimental liver fibrosis. The up-regulation of the ligand Slit2 and membrane receptor Robo2 genes within this pathway was further validated in TAA-induced fibrotic livers. By immunofluorescence staining, Robo2 was localized in fibrotic septa of fibrotic liver and on the surface of HSCs. By Western blot analysis, recombinant Slit2 (rSlit2) was found to promote fibrogenic protein expression in JS1 cells, an immortalized mouse HSC line, while activating PI3K/Akt signaling pathway. This effect was abrogated by LY294002, a PI3K/Akt pathway inhibitor. In addition, rSlit2 stimulation markedly inhibited JS1 cells migration in transwell migration assays, which was abrogated by small interfering RNA (siRNA) knockdown of Robo2 in the cells. SIGNIFICANCE: 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.

Outcome of Peroral Endoscopic Myotomy (POEM) for Treating Achalasia Compared With Laparoscopic Heller Myotomy (LHM).

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.