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Gastric cancer remains a significant global health challenge, causing a substantial number of cancer-related deaths, particularly in China. While the exact causes of gastric cancer are still being investigated, Helicobacter pylori (H. pylori) infection has been identified as the primary risk factor, which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time. Since the 1990s, numerous efforts have focused on assessing the effectiveness of H. pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment. This body of work, including several community-based interventions and meta-analyses, has shown a reduction in both the incidence of and mortality from gastric cancer following H. pylori treatment, alongside a decreased risk of metachronous gastric cancer. In this review, we seek to consolidate current knowledge on the effects of H. pylori treatment on gastric cancer prevention, its systemic consequences, cost-effectiveness, and the influence of antibiotic resistance and host characteristics on treatment outcomes. We further discuss the potential for precision primary prevention of H. pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.

Abstract Objective Screening and early diagnosis of gastric cancer (GC) are crucial for improved prognosis. However, gastroscopic screening is not feasible in large populations due to its high cost and invasive nature. The detection of circulating cell‐free DNA (cfDNA) provides an attractive minimally‐invasive alternative for screening of GC. In this systematic review and meta‐analysis, we evaluate the diagnostic value of cfDNA‐based markers for GC, including the detection of total concentration, mutations, and methylation alterations. Methods We performed a systematic search of four literature databases (PubMed, Embase, Web of Science, and Cochrane Library) for articles published before November 2022. The revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) was used to evaluate the quality of included studies. PROSPERO registration number: CRD42021210830. Results A total of 15 original articles involving 2849 individuals were included in this meta‐analysis, comprising five studies on concentration, nine studies on methylation alterations, and one study on mutation biomarkers of cfDNA. Among these studies, seven selected early‐stage GC subjects. For the diagnoses of overall stages and early‐stage GC, the pooled sensitivities with 95% confidence interval were 0.74 (0.66–0.82) and 0.64 (0.51–0.76), and the pooled specificities were 0.92 (0.84–0.96) and 0.94 (0.87–0.98) with summary areas under the curve (SAUCs) of 0.89 (0.86–0.91) and 0.86 (0.83–0.89), respectively. Conclusions This meta‐analysis suggests that cfDNA‐based biomarkers show diagnostic value for GC early detection.

Abstract Background Effective noninvasive biomarkers of gastric cancer (GC) are critical for early detection and improvement of prognosis. We performed genome‐wide long non‐coding RNA (lncRNA) microarray analysis to identify and validate novel GC biomarkers depending on a high‐risk population cohort. Methods LncRNA profiles were described using the Human LncRNA Microarray between GC and control plasma samples. The differential candidate lncRNAs were validated in two stages by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). We further evaluated the joint effect between the GC‐associated lncRNA and Helicobacter pylori (H. pylori) infection on the risk of cardia and non‐cardia GC, respectively. Results Different lncRNA expression profiles were identified between GC and control plasma with a total of 1206 differential lncRNAs including 470 upregulated and 736 downregulated in GC compared with the control group. The eight significantly upregulated lncRNAs (RP11‐521D12.1, AC011995.3, RP11‐5P4.3, RP11‐244 K5.6, RP11‐422 J15.1, CTD‐2306 M5.1, CTC‐428G20.2, and AC009133.20) in GC cases both in the present study and a similar microarray screening study by our collaborative team were selected for a two‐stage validation. After the large sample size validation, the subjects with higher expression of RP11‐244 K5.6 showed a significantly increased risk of GC with an adjusted odds ratio (OR) as 2.68 and 95% confidence interval (CI) as 1.15–6.24. Joint effects between RP11‐244 K5.6 expression and H. pylori infection on the risk of GC were evaluated with no statistical significance. Conclusions Our study found different lncRNA expression profiles between GC and control plasma and preliminarily identified RP11‐244 K5.6 as a potential noninvasive biomarker for GC screening.

Objective: This study aimed at examining the alterations in metabolomic profiles caused by treatment of H. pylori infection, and the associations between key plasma metabolites and the risk of gastric lesion progression during follow-up after treatment. Methods: An intervention trial was performed in 183 participants, 117 of whom were H. pylori positive participants receiving treatment for H. pylori infection. H. pylori positive participants were prospectively followed for 182 to 1,289 days. Untargeted metabolomics assays were conducted on plasma samples collected at baseline, 6 months after treatment, and during continued follow-up. Results: We identified 59 metabolites with differential posttreatment changes between participants with successful and failed H. pylori eradication, 17 metabolites significantly distinguished participants with successful vs. failed eradication. Two metabolites [PC(18:1(11Z)/14:1(9Z)) and (2S)-6-amino-2-formamidohexanamide] showed posttreatment changes positively associated with successful H. pylori eradication, and were inversely associated with the risk of gastric lesion progression among participants with successful eradication. In contrast, 9-decenoic acid showed posttreatment changes inversely associated with successful eradication: its level was positively associated with the risk of gastric lesion progression among participants with successful eradication. Although the identified metabolites showed a temporary but significant decline after treatment, the trend generally reversed during continued follow-up, and pretreatment levels were restored. Conclusions: Treatment of H. pylori infection significantly altered plasma metabolic profiles in the short term, and key metabolites were capable of distinguishing participants with successful vs. failed eradication, but might not substantially affect metabolic regulation in the long term. Several plasma metabolites were differentially associated with the risk of gastric lesion progression among participants with successful or failed eradication.

Platelets are blood cells that are primarily produced by the shedding of megakaryocytes in the bone marrow. Platelets participate in a variety of physiological and pathological processes in vivo, including hemostasis, thrombosis, immune-inflammation, tumor progression, and metastasis. Platelets have been widely used for targeted drug delivery therapies for treating various inflammatory and tumor-related diseases. Compared to other drug-loaded treatments, drug-loaded platelets have better targeting, superior biocompatibility, and lower immunogenicity. Drug-loaded platelet therapies include platelet membrane coating, platelet engineering, and biomimetic platelets. Recent studies have indicated that platelet extracellular vesicles (PEVs) may have more advantages compared with traditional drug-loaded platelets. PEVs are the most abundant vesicles in the blood and exhibit many of the functional characteristics of platelets. Notably, PEVs have excellent biological efficacy, which facilitates the therapeutic benefits of targeted drug delivery. This article provides a summary of platelet and PEVs biology and discusses their relationships with diseases. In addition, we describe the preparation, drug-loaded methods, and specific advantages of platelets and PEVs targeted drug delivery therapies for treating inflammation and tumors. We summarize the hot spots analysis of scientific articles on PEVs and provide a research trend, which aims to give a unique insight into the development of PEVs research focus.

Objective: Upper gastrointestinal (UGI) cancers, predominantly gastric cancer (GC) and esophageal cancer (EC), are malignant tumor types with high morbidity and mortality rates. Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years. In this systematic review, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC. Methods: A systematic search of three databases (Embase, PubMed, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included articles. Results: A total of 52 original studies were included for review. A number of metabolites were differentially distributed between GC and EC cases and non-cases, including those involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and protein and lipid metabolism. Lactic acid, glucose, citrate, and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine, glutamate, and valine were among the most commonly reported amino acids. The lipid metabolites identified previously included saturated and unsaturated free fatty acids, aldehydes, and ketones. However, the key findings across studies to date have been inconsistent, potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. Conclusions: Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers, supporting the potential of applying metabolomic profiling in cancer prevention and management efforts.

Macrophages, mainly divided into M1 pro-inflammatory and M2 anti-inflammatory types, play a key role in the transition from inflammation to repair after trauma. In chronic inflammation, such as diabetes and complex bone injury, or the process of certain inflammatory specific emergencies, the ratio of M1/M2 cell populations is imbalanced so that M1-macrophages cannot be converted into M2 macrophages in time, resulting in delayed trauma repair. Early and timely transformation of macrophages from the pro-inflammatory M1-type into the pro-reparative M2-type is an effective strategy to guide trauma repair and establish the original homeostasis. We prepared purified nano-platelet vesicles (NPVs) and assessed their effects on macrophage phenotype switching through transcriptome analysis. The results elucidate that NPVs promote pathways related to angiogenesis, collagen synthesis, cell adhesion, and migration in macrophages, and we speculate that these advantages may promote healing in traumatic diseases.

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.

BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP) assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC) samples (36/40) was significantly higher than that observed in gastritis (19/45) or normal samples (7/13) (P

BACKGROUND:Mutation of Wnt signal antagonists Apc or Axin activates beta-catenin signaling in many cancers including the majority of human colorectal adenocarcinomas. The phenotype of apc or axin mutation in the fruit fly Drosophila melanogaster is strikingly similar to that caused by mutation in the segment-polarity gene, naked cuticle (nkd). Nkd inhibits Wnt signaling by binding to the Dishevelled (Dsh/Dvl) family of scaffold proteins that link Wnt receptor activation to beta-catenin accumulation and TCF-dependent transcription, but human NKD genes have yet to be directly implicated in cancer. METHODOLOGY/PRINCIPAL FINDINGS:We identify for the first time mutations in NKD1--one of two human nkd homologs--in a subset of DNA mismatch repair-deficient colorectal tumors that are not known to harbor mutations in other Wnt-pathway genes. The mutant Nkd1 proteins are defective at inhibiting Wnt signaling; in addition, the mutant Nkd1 proteins stabilize beta-catenin and promote cell proliferation, in part due to a reduced ability of each mutant Nkd1 protein to bind and destabilize Dvl proteins. CONCLUSIONS/SIGNIFICANCE:Our data raise the hypothesis that specific NKD1 mutations promote Wnt-dependent tumorigenesis in a subset of DNA mismatch-repair-deficient colorectal adenocarcinomas and possibly other Wnt-signal driven human cancers.

The effects of a 7.3-y supplementation with garlic and micronutrients and of anti-He/icobacter pylon treatment with amoxicillin (1 g twice dailyl and omeprazole (20 mg twice daily) on serum folate, vitamin 8-12, homocysteine, and glutathione concentrations were assessed in a rural Chinese population. A randomized, double-blind, placebo-controlled, factorial trial was conducted to compare the ability of 3 treatments to retard the development of precancerous gastric lesions in 3411 subjects. The treatments were: 11 anti-H. pylon treatment with amoxicillin and omeprazole; 2) 7.3-y supplementation with aged garlic and steam-distilled garlic oil; and 3) 7.3-y supplementation with vitamin C, vitamin E, and selenium. All 3 treatments were given in a 2~ factorial design to subjects seropositive for H. pyloriinfection; only the garlic supplement and vitamin and selenium supplement were given in a 22 factorial design to the other sublects. Thirty-four subjects were randomly selected from each of the 12 treatment strata. Sera were analyzed after 7.3 y to measure effects on folate, vitamin B-i 2, homocysteine, and glutathione concentrations. Regression analyses adjusted for age, gender, and smoking indicated an increase of 10.2% (95%Cl: 2.9-i 8.1%) in serum folate after garlic supplementation and an increase of 13.4% l95%Cl: 5.3-22.2%) in serum glutathione after vitamin and selenium supplementation. The vitamin and selenium supplement did not affect other analytes and the amoxicillin and omeprazole therapy did not affect any of the variables tested. In this rural Chinese population, 7.3 y of garlic supplementation increased the serum folate concentration and the vitamin and selenium supplement increased that of glutathione, but neither affected serum concentrations of vitamin 6-12 or homocysteine. J. Nutr. 139: 106-112, 2009. [ABSTRACT FROM AUTHOR]

The article discusses the result of a study concerning genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma (SGC) in Chinese populations. It was found that the -347del allele of E-cadherin links with the +178T and +234 13N ins alleles and that the -347 del/del genotype may increase the susceptibility of SGC among males in high-risk area.

Helicobacter pyloriinfection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression ofH. pyloriin an endemically infected population at high risk for gastric cancer.A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 ± 11.2 years (mean± SD) withH. pyloriinfection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree ofH. pyloriinfection was determined using the13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection.A total of 189 subjects with positive13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05).Regular consumption of cranberry juice can suppressH. pyloriinfection in endemically afflicted populations. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor a (TNFa), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.273.21] or IL-10-1082 G (OR 2.02; 95% CI 1.243.29) or TNFa-308 AG (OR 1.81; 95% CI 1.043.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.384.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.424.93). An increased OR was also suggested for IL-1B-31 and TNFa-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFa may play important roles in developing gastric cancer in the Chinese population. [ABSTRACT FROM AUTHOR]