ABSTRACT
BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.
ABSTRACT
Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.
Subject(s)
Anti-Bacterial Agents , Furazolidone , Helicobacter Infections , Helicobacter pylori , Furazolidone/therapeutic use , Furazolidone/administration & dosage , Helicobacter Infections/drug therapy , Humans , Helicobacter pylori/drug effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/administration & dosage , Drug Therapy, Combination , Drug Resistance, Bacterial , Treatment OutcomeABSTRACT
BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Proton Pump Inhibitors/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Bismuth/therapeutic use , Amoxicillin/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Drug Therapy, Combination , Amoxicillin/therapeutic use , Proton Pump Inhibitors/therapeutic use , Body Size , Body Weight , Treatment Outcome , Clarithromycin/therapeutic useABSTRACT
OBJECTIVE: The role of urgent endoscopy in nonvariceal upper gastrointestinal hemorrhage (NVUGIH) remains controversial. We designed a retrospective study to compare the outcomes between urgent endoscopy (within 12 h) and non-urgent endoscopy for patients with NVUGIH. METHODS: A total of 540 hospitalized patients with NVUGIH were included in our study. Patients who received endoscopy within 12 h or after 12 h were divided into two groups, the urgent and non-urgent endoscopy groups, respectively. The clinical outcomes including rebleeding, mortality, endoscopic re-intervention, need for emergency surgery and interventional radiotherapy were compared between the groups. Patients with Glasgow-Blatchford scores (GBS) <12 and ≥12 were defined as the lower- and high-risk groups, respectively, and the predictors of rebleeding and mortality in both groups were analyzed individually. RESULTS: Patients with NVUGIH in the urgent endoscopy group had a higher rate of rebleeding (27.6% vs. 16.9%, P=0.003) and blood transfusion (73.2% vs. 55.5%, P<0.001) than those in the non-urgent endoscopy group, while the mortality and the length of hospitalization were not significantly different between the groups (P>0.05). For lower-risk patients, urgent endoscopy was independently associated with a higher likelihood of rebleeding (adjusted OR: 1.73, 95% CI: 1.03-2.88), while it was not associated with in-hospital mortality. However, the urgent need for endoscopy was not associated with rebleeding and inhospital mortality in high-risk patients. CONCLUSION: Endoscopy within 12 h did not provide any advantage in the outcomes of patients with NVUGIH, and may even lead to an increased rebleeding rate in lower-risk patients.
Subject(s)
Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/surgery , Hospital Mortality , Hospitalization , Humans , Retrospective StudiesABSTRACT
Aim: Different researches showed controversial results about the 'off-hours effect' in nonvariceal upper gastrointestinal bleeding (NVUGIB). Materials & methods: A total of 301 patients with NVUGIB were divided into regular-hours group and off-hours group based on when they received endoscopic hemostasis, and the relationship of the clinical outcomes with off-hours endoscopic hemostasis was evaluated. Results: Patients who received off-hours endoscopy were sicker and more likely to experience worse clinical outcomes. Off-hours endoscopic hemostasis was a significant predictor of the composite outcome in higher-risk patients (adjusted OR: 4.63; 95% CI: 1.35-15.90). However, it did not associate with the outcomes in lower-risk patients. Conclusion: Off-hours effect may affect outcomes of higher-risk NVUGIB patients receiving endoscopic hemostasis (GBS ≥12).
Subject(s)
Hemostasis, Endoscopic , Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage/therapy , Hemostasis, Endoscopic/methods , HumansABSTRACT
OBJECTIVE: Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD: Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS: A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION: High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Amoxicillin , Anti-Bacterial Agents/adverse effects , Bismuth/adverse effects , Drug Therapy, Combination , Esomeprazole/pharmacology , Esomeprazole/therapeutic use , Helicobacter Infections/drug therapy , Humans , Prospective Studies , Proton Pump Inhibitors/adverse effects , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to investigate risk factors and psychological stress of health-care workers (HCWs) with coronavirus disease 2019 (COVID-19) in a nonfrontline clinical department. METHODS: Data of 2 source patients and all HCWs with infection risk were obtained in a department in Wuhan from January to February 2020. A questionnaire was designed to evaluate psychological stress of COVID-19 on HCWs. RESULTS: The overall infection rate was 4.8% in HCWs. Ten of 25 HCWs who contacted with 2 source patients were diagnosed with confirmed COVID-19 (8/10) and suspected COVID-19 (2/10). Other 2 HCWs were transmitted by other patients or colleagues. Close care behaviors included physical examination (6/12), life nursing (4/12), ward rounds (4/12), endoscopic examination (2/12). Contacts fluctuated from 1 to 24 times and each contact was short (8.1 min ± 5.6 min). HCWs wore surgical masks (11/12), gloves (7/12), and isolation clothing (3/12) when providing medical care. Most HCWs experienced a mild course with 2 asymptomatic infections, taking 9.8 d and 20.9 d to obtain viral shedding and clinical cure, respectively. Psychological stress included worry (58.3%), anxiety (83.3%), depression (58.3%), and insomnia (58.3%). CONCLUSIONS: Close contact with COVID-19 patients and insufficient protection were key risk factors. Precaution measures and psychological support on COVID-19 is urgently required for HCWs.
Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , COVID-19/epidemiology , SARS-CoV-2 , Health Personnel/psychology , Stress, Psychological/etiology , MasksABSTRACT
BACKGROUND: Epigenetic dysregulation participates in the initiation and progression of hepatocellular carcinoma (HCC). Bromodomain-containing protein 9 (BRD9) can identify acetylated lysine residues, contributing to several cancers. The function and molecular mechanism of BRD9 in HCC remain poorly understood. METHODS: BRD9 levels in tissues and cells of HCC and normal liver were evaluated using bioinformatic analysis, real-time PCR, and western blot. BRD9's association with clinical outcomes was investigated via survival analyses. Biological behaviors and pathways related to BRD9 were predicted using gene set enrichment analysis. BRD9's role in proliferation was verified via cell counting kit 8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays. Its role in the cell cycle and apoptosis was assessed using flow cytometry. The role of BRD9 in vivo was investigated using xenograft tumor models. A rescue assay was performed to investigate the molecular mechanism of BRD9. RESULTS: BRD9 was markedly upregulated in HCC and higher BRD9 expression was associated with higher grade, advanced stage, greater tumor size, and poorer prognosis. BRD9 overexpression enhanced cell proliferation, cell cycle progress, but impeded cell apoptosis. BRD9 downregulation had the opposite effects. In vivo, BRD9 promoted xenograft tumor growth. Mechanistically, BRD9 activated Wnt/ß-catenin signaling, obstruction of which abrogated BRD9-mediated tumorigenesis. CONCLUSION: Increased BRD9 in HCC correlated with poor prognosis, which functioned via activating Wnt/ß-catenin signaling. Thus, BRD9 might be a promising biomarker and therapeutic target for patients with HCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Transcription Factors/metabolism , Wnt Signaling Pathway , beta Catenin/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Cycle , Cell Movement , Cell Proliferation , Female , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Transcription Factors/genetics , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Young Adult , beta Catenin/geneticsABSTRACT
Background: Increasing evidence has implicated that lncRNAs (long non-coding RNAs) play significant roles in carcinogenesis and progression of HCC (hepatocellular carcinoma). LINC01503 is a new lncRNA related to several tumors. Nonetheless, its role in HCC still remains unclear. Methods: The expression levels of LINC01503 in HCC, normal liver tissues as well as HCC cell lines were evaluated by TCGA (The Cancer Genome Atlas) and real-time PCR assay, respectively. The relationship between LINC01503 levels and the prognosis of patients with HCC was evaluated using Kaplan-Meier survival analysis. Then the potential biological functions and pathways related to LINC01503 were investigated by GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, and GSEA v4.0.1 software was employed. Furthermore, the influence of LINC01503 on the proliferation and apoptosis of HCC cells was confirmed using CCK8 assay, flow cytometry, and clone formation assay in cell experiments. Also the pro-tumor effect of LINC01503 was verified by mice xenograft experiment in vivo. In addition, the functional pathway of LINC01503 was proved by western blot and rescue experiments. Results: LINC01503 was highly expressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage, and poor prognosis of HCC patients. Silencing LINC01503 with shRNA significantly restrained the proliferation of MHCC-97H HCC cells and strengthened the apoptosis, while up-regulation of LINC01503 in Huh7 HCC cells contributed to the contrary effects. Besides, LINC01503 promoted tumor growth of nude mice transplanted with liver cancer cells. Mechanistically, MAPK/ERK signaling pathway was activated by LINC01503, inhibition of which could alleviate the pro-tumor effect of LINC01503, consistent with the forecast of GSEA (Gene Set Enrichment Analysis). Conclusion: LINC01503 is highly expressed in HCC and promotes the progression of HCC via MAPK/ERK pathway, which maybe a new potential biomarker and therapeutic target for HCC.