Impact of body size on efficacy of high-dose dual therapy for Helicobacter pylori eradication.

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.

Urgent Endoscopy in Nonvariceal Upper Gastrointestinal Hemorrhage: A Retrospective Analysis.

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.

Does off-hours endoscopic hemostasis affect outcomes of nonvariceal upper gastrointestinal bleeding?

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).

Infection, Screening, and Psychological Stress of Health-Care Workers With COVID-19 in a Nonfrontline Clinical Department.

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.

Bromodomain-containing protein 9 promotes hepatocellular carcinoma progression via activating the Wnt/ß-catenin signaling pathway.

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.

LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.

Long non-coding RNA LINC01503 promotes the progression of hepatocellular carcinoma via activating MAPK/ERK pathway.

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.

Primary Cilia Blockage Promotes the Malignant Behaviors of Hepatocellular Carcinoma via Induction of Autophagy.

Primary cilia are organelles protruding from cell surface into environment that function in regulating cell cycle and modulating cilia-related signal. Primary ciliogenesis and autophagy play important roles in tumorigenesis. However, the functions and interactions between primary cilia and autophagy in hepatocellular carcinoma (HCC) have not been reported yet. Here, we aimed to investigate the relationship and function of primary cilia and autophagy in HCC. In vitro, we showed that serum starvation stimuli could trigger primary ciliogenesis in HCC cells. Blockage of primary ciliogenesis by IFT88 silencing enhanced the proliferation, migration, and invasion ability of HCC cells. In addition, inhibition of primary cilia could positively regulate autophagy. However, the proliferation, migration, and invasion ability which were promoted by IFT88 silencing could be partly reversed by inhibition of autophagy. In vivo, interference of primary cilia led to acceleration of tumor growth and increase of autophagic flux in xenograft HCC mouse models. Moreover, IFT88 high expression or ATG7 low expression in HCC tissues was correlated with longer survival time indicated by the Cancer Genome Atlas (TCGA) analysis. In conclusion, our study demonstrated that blockage of primary ciliogenesis by IFT88 silencing had protumor effects through induction of autophagy in HCC. These findings define a newly recognized role of primary cilia and autophagy in HCC.

Circular RNAs in digestive system cancer: potential biomarkers and therapeutic targets.

Circular RNAs (circRNAs) are a series of special closed circular RNA molecules with stability and conservatism. In recent years, advances in high-throughput RNA sequencing technology have led to explosive discovery of circRNAs in different types of species and cells. Moreover, circRNAs can accomplish a remarkable multitude of biological functions, such as regulating transcription or splicing, serving as miRNA sponges, interacting with RNA-binding proteins, and translating proteins. Meanwhile, circRNAs involve in the biogenesis and development of many diseases, including cardiovascular disorders, nervous system disorders, cancers, etc. Herein, we discuss the latest research progress of circRNA, as well as their diagnostic and prognostic significance in digestive system cancers. In addition, this paper highlights that circRNAs might serve as potential therapeutic targets for novel drugs by taking digestive system cancer as an illustrative example.