Association of per- and polyfluoroalkyl substances with constipation: The National Health and Nutrition Examination Survey (2005-2010).

BACKGROUND: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood. OBJECTIVE: This study seeks to explain the relationship between PFAS and constipation. METHODS: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables. RESULTS: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 µg/L) compared to those without constipation (23.30 µg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation. CONCLUSION: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation.

Diagnostic value of cavernous sinus swelling and extrusion sign in cavernous sinus hemangioma.

BACKGROUND AND PURPOSE: To examine the diagnostic value of imaging features in cavernous sinus hemangioma (CSH). MATERIALS AND METHODS: The clinical and imaging data of patients with pathologically confirmed CSH, cavernous sinus meningioma, trigeminal schwannoma and pituitary adenoma invading the cavernous sinus between May 2017 and May 2022 were retrospectively analyzed. The cases were divided into the CSH and non-CSH groups to summarize the magnetic resonance imaging (MRI) characteristics of CSH. Univariate χ2 analysis was performed to assess five indexes, including signal intensity on T2WI, homogeneity of T2WI, enhancement of enhanced T1, enhanced T1 with dural tail sign, and cavernous sinus swelling and extrusion sign. RESULTS: There were significant differences in four features, including hyperintensity on T2WI, homogeneity of T2WI, T1-enhanced without meningeal tail sign, and cavernous sinus swelling and extrusion sign between the CSH and non-CSH groups, with cavernous sinus swelling and extrusion sign showing the most pronounced distinction, with a sensitivity of 100%, a specificity of 93.02%, and an accuracy of 94.23%. The four features could be jointly used as diagnostic criteria, with a sensitivity of 94.44%, a specificity of 100.00%, and an accuracy of 99.04%. CONCLUSION: Cavernous sinus swelling and extrusion sign is a reliable imaging index for CSH diagnosis. Homogenous hyperintensity or marked hyperintensity on T2WI, enhanced T1 without dural tail sign, and cavernous sinus swelling and extrusion sign could be jointly used as diagnostic criteria, which may improve the accuracy of CSH diagnosis.

Review of dietary patterns and gastric cancer risk: epidemiology and biological evidence.

Due to rapid research expansion on dietary factors and development of cancer prevention guidelines, the field of dietary pattern and its relationship to cancer risk has gained more focus. Numerous epidemiology studies have reported associations between Gastric Cancer (GC) and both data-driven posteriori dietary pattern and priori dietary pattern defined by predetermined dietary indexes. As dietary patterns have evolved, a series of patterns based on biological markers has advanced, offering deeper insights into the relationship between diet and the risk of cancer. Although researches on dietary patterns and cancer risk are booming, there is limited body of literature focusing specifically on GC. In this study, we compare the similarities and differences among the specific components of dietary patterns and indices, summarize current state of knowledge regarding dietary patterns related to GC and illustrate their potential mechanisms for GC prevention. In conclusion, we offer suggestions for future research based on the emerging themes within this rapidly evolving field.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

BACKGROUND: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. METHODS: qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. RESULTS: The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. CONCLUSIONS: The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Modified Selective Dorsal Rhizotomy Exposure Method for Adults With Spastic Paralysis of the Lower Limbs.

BACKGROUND AND OBJECTIVES: Spinal deformities are a common complication after selective dorsal rhizotomy (SDR). In this article, we introduce a more minimally invasive SDR procedure in adult patients with spastic paralysis of the lower limbs. METHODS: In this retrospective analysis of SDR in 8 adult patients with spastic paralysis of the lower limbs, a modified exposure method was used during the surgery. Only the lower part of the L1 spinous process, upper part of the L2 spinous process, and part of the lamina were resected through L1-2 interlaminar approaches. The motor and sensory roots were found to be completely dependent on electrophysiological monitoring. The sensory roots of the target muscle groups were partially transected. All patients were followed up for 2-4 years. The degree of lower extremity spasm was assessed using the Gross Motor Function Classification Scale, Ashworth grading, Gross Motor Function Measure-66, joint range of motion, and electromyography analysis. RESULTS: All 8 patients were successfully operated with the help of intraoperative electrophysiological monitoring. The Ashworth score of the target muscles, Gross Motor Function Measure-66 score, and range of motion of the joints improved significantly after surgery. Two patients achieved cross-grade improvement in their Gross Motor Function Classification Scale scores. No persistent incision pain or spinal deformities were observed during follow-up. CONCLUSION: The interspinous process approach provides sufficient surgical space and reduced the damage to the bone structure of the spine. The electrophysiological monitoring protocol is suitable for adult patients with lower extremity spasm.

New insight into circRNAs: characterization, strategies, and biomedical applications.

Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism. Increasing evidence has revealed that circRNAs participate in diverse cellular processes, and their dysregulation is involved in the pathogenesis of various diseases, particularly cancer. In this review, we systematically discuss the characterization of circRNAs, databases, challenges for circRNA discovery, new insight into strategies used in circRNA studies and biomedical applications. Although recent studies have advanced the understanding of circRNAs, advanced knowledge and approaches for circRNA annotation, functional characterization and biomedical applications are continuously needed to provide new insights into circRNAs. The emergence of circRNA-based protein translation strategy will be a promising direction in the field of biomedicine.

METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6 A homeostasis.

N6 -Methyladenosine (m6 A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6 A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6 A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6 A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6 A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6 A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.

An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis.

BACKGROUND: Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC. METHODS: The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations. RESULTS: A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC. CONCLUSIONS: FMT can achieve clinical remission and clinical response in patients with UC.

A reliable nomogram model for predicting esophageal stricture after endoscopic submucosal dissection.

ABSTRACT: Currently, endoscopic submucosal dissection (ESD) has gradually become the diagnosis and treatment of choice for initial esophageal cancer. However, the formation of esophageal stricture after ESD is one of its important complications. In this paper, we intend to identify the risk factors of esophageal stricture to develop a nomogram model to predict the risk of esophageal stricture and validate this model.A total, 159 patients were included in this study, including 21 patients with esophageal stenosis. Multivariate analysis showed that age greater than 60 years, high neutrophil-to-lymphocyte ratio, the extent of esophageal mucosal defect greater than 1/2, and postoperative pathological type of early esophageal squamous cell carcinoma were independent risk factors for predicting esophageal stricture. We constructed a nomogram model to predict esophageal stenosis by these 4 independent predictors.The prediction performance of the model was verified by the area under the receiver operating characteristic curve, the area under the receiver operating characteristic curve of the model was 0.889, and the sensitivity and specificity were 80.00% and 91.28%, respectively, indicating that the prediction performance of the model was good; The calibration curve constructed by internal cross-validation suggested that the predicted results of the nomogram agreed well with the actual observed values.The nomogram model has a high accuracy for predicting esophageal stricture after esophageal ESD and is extremely important to reduce or avoid the occurrence of esophageal stricture. But it needs more external and prospective validation.

Relationship between self-care compliance, trust, and satisfaction among hypertensive patients in China.

Introduction: Hypertension is a growing public health concern worldwide. It is a leading risk factor for all-cause mortality and may lead to complications such as cardiovascular disease, stroke, and kidney failure. Poor compliance of hypertensive patients is one of the major barriers to controlling high blood pressure. Compliance is not ideal among Chinese patients, and increasing patient self-care compliance with hypertension is necessary. Methods: This article analyzes the status of self-care compliance, trust, and satisfaction among Chinese hypertensive patients using cross-sectional data from Zhejiang Province. We use a multi-group structural equation model (MGSEM) to compare the interrelationships across genders. Results: The study's findings show that the average trust, satisfaction, and compliance scores are 3.92 ± 0.55, 3.98 ± 0.61, and 3.33 ± 0.41, respectively. Female patients exhibit higher average total scores for trust and compliance than male patients. The SEM results indicate that trust has a direct positive association with compliance [ß = 0.242, 95% CI: (0.068, 0.402)] and satisfaction [ß = 0.260, 95% CI: (0.145, 0.367)], while their satisfaction is not directly associated with compliance. The results of MGSEM show that trust has an indirect effect on compliance in the male group through satisfaction [ß = 0.051, P < 0.05, 95% CI: (0.012, 0.116)]. In the female group, trust has a direct effect on satisfaction [ß = 0.235, P < 0.05, 95% CI: (0.041, 0.406)] and compliance [ß = 0.319, P < 0.01, 95% CI: (0.086, 0.574)]. Discussion: This study reveals the mechanisms of self-care compliance, trust, and satisfaction among Chinese hypertensive patients. Its findings may serve as a reference for guiding primary healthcare providers to improve hypertension patients' compliance and implement gender-targeted health interventions.

The Application of Induced Pluripotent Stem Cells Against Liver Diseases: An Update and a Review.

Liver diseases are a major health concern globally, and are associated with poor survival and prognosis of patients. This creates the need for patients to accept the main alternative treatment of liver transplantation to prevent progression to end-stage liver disease. Investigation of the molecular mechanisms underpinning complex liver diseases and their pathology is an emerging goal of stem cell scope. Human induced pluripotent stem cells (hiPSCs) derived from somatic cells are a promising alternative approach to the treatment of liver disease, and a prospective model for studying complex liver diseases. Here, we review hiPSC technology of cell reprogramming and differentiation, and discuss the potential application of hiPSC-derived liver cells, such as hepatocytes and cholangiocytes, in refractory liver-disease modeling and treatment, and drug screening and toxicity testing. We also consider hiPSC safety in clinical applications, based on genomic and epigenetic alterations, tumorigenicity, and immunogenicity.

Gastric cancer-associated microRNA expression signatures: integrated bioinformatics analysis, validation, and clinical significance.

BACKGROUND: Gastric cancer (GC) is one of the common gastrointestinal malignancy worldwide and exhibits a poor prognosis. Increasing studies have indicated that microRNAs play critical roles in the cancer progression and have shown great potential as useful biomarkers. The search for potential diagnostic and prognostic biomarkers of gastric cancer (GC) with integrated bioinformatics analyses has been undertaken in previous studies. METHODS: In this study, the robust rank aggregation (RRA) method was used to perform an integrated analysis of differentially expressed miRNAs (DEMs) from five microarray datasets in the Gene Expression Omnibus (GEO) database to find robust biomarkers for GC. Ultimately, seven miRNAs were filtered from fourteen primary miRNAs using the validation set of The Cancer Genome Atlas (TCGA) database. Based on these results, diagnostic and survival analyses were performed, and logistic regression and Cox regression were used to determine the clinicopathological characteristics of the DEM expression and overall survival. RESULTS: Nine eligible miRNA datasets related to GC were selected from the GEO database for integrated analysis in this study. Diagnostic analysis implied that these miRNAs could be regarded as promising candidate diagnostic biomarkers in GC tissues, but whether the results of the tissue analysis are consistent with those of peripheral blood analysis requires further validation. The logistic regression indicated that the ectopic expression of these DEMs was relevant to the histological type, anatomical region, and pathological grade of GC. However, the survival and Cox regression analyses suggested that the poor prognosis of GC patients was not strongly dependent on the ectopic expression of the seven miRNAs, but rather, a poor prognosis was associated with age, metastasis, and histological grade. CONCLUSIONS: Based on the results presented in this study it can be concluded that these miRNAs (miR-455-3p, miR-135b-5p, let-7a-3p, miR-195-5p, miR-204-5p, miR-149-5p, and miR-143-3p) might be potential biomarkers for the early diagnosis of GC patients, but this finding should be regarded with caution. A large-scale, prospective, and multicenter cohort study should be performed.

Prevalence and risk factors of Helicobacter pylori infection in Wuwei, a high-risk area for gastric cancer in northwest China: An all-ages population-based cross-sectional study.

OBJECTIVE: This study aimed to determine the prevalence and risk factors of Helicobacter pylori infection across all age groups in Wuwei City, a high-risk area for gastric cancer in Northwest China. METHODS: We conducted this study from 2016 to 2017 in an urban and a rural community in Wuwei City. Stool antigen tests targeted individuals aged 0 to 3 years old, and 13 C-urea breath tests targeted individuals aged above 3 years. We selected participants based on hierarchical cluster sampling. We assessed the association between variables and H. pylori infection based on logistic regression models. RESULTS: Ultimately, the results of 2,163 participants (age: 0 to 77 years old) were included (1,238 minors and 925 adults) in the analysis. The overall prevalence of H. pylori infection was 35.6%. It increased with age, reaching the peak in the 30 to 39 age group, and then began to decline. In multivariate analysis, age was positively associated with prevalence of H. pylori infection, and factors negatively associated with the prevalence were drinking running water, the frequency of yoghurt consumption, and an annual household income of Renminbi (¥) 30,000-100,000 or 100,000 above. In the subgroup analyses, however, the same variables associated differently in different age groups. Additionally, we interestingly noticed that boarding, eating at school cafeterias over six times per week, and frequently drinking untreated water were independent predictors of H. pylori infection in junior and senior high school students. CONCLUSION: The prevalence of H. pylori infection is moderate and closely associated with the socioeconomic conditions of Wuwei City, as well as the sanitary situations and dietary habits of the participants in the city. Boarding, eating at school, and drinking untreated water are the main factors explaining the rising infection rate in junior-senior high school students.

A Novel Six-Gene-Based Prognostic Model Predicts Survival and Clinical Risk Score for Gastric Cancer.

Background: Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related genes (ARGs) have rarely been analyzed in gastric cancer (GC). The purpose of this study was to analyze ARGs in GC using bioinformatic analysis and to identify new biomarkers for predicting the overall survival (OS) of patients with GC. Methods: The gene expression profiles and clinical data of patients with GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and ARGs were obtained from two other datasets (the Human Autophagy Database and Molecular Signatures Database). Lasso, univariate, and multivariate Cox regression analyses were performed to identify the OS-related ARGs. Finally, a six-ARG model was identified as a prognostic indicator using the risk-score model, and survival and prognostic performance were analyzed based on the Kaplan-Meier test and ROC curve. Estimate calculations were used to assess the immune status of this model, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed for investigating the functions and terms associated with the model-related genes in GC. Results: The six ARGs, DYNLL1, PGK2, HPR, PLOD2, PHYHIP, and CXCR4, were identified using Lasso and Cox regression analyses. Survival analysis revealed that the OS of GC patients in the high-risk group was significantly lower than that of the low-risk group (p < 0.05). The ROC curves revealed that the risk score model exhibited better prognostic performance with respect to OS. Multivariate Cox regression analysis indicated that the model was an independent predictor of OS and was not affected by most of the clinical traits (p < 0.05). The model-related genes were associated with immune suppression and several biological process terms, such as extracellular structure organization and matrix organization. Moreover, the genes were associated with the P13K-Akt signaling pathway, focal adhesion, and MAPK signaling pathway. Conclusions: This study presents potential prognostic biomarkers for GC patients that would aid in determining the best patient-specific course of treatment.

Prevalence and associated risk factors of Helicobacter pylori infection in the Wuwei cohort of north-western China.

OBJECTIVES: To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer. METHODS: Helicobacter pylori infection was analysed in 21 291 adults by 14 C-urea breath test, and H. pylori antibody were detected in 9183 serum samples by latex immunoturbidimetric method. The correlation of H. pylori infection with demographic-economic, lifestyle factors and medical history among the participants was determined by questionnaire. The antibodies against H. pylori urease, VacA and CagA in serum were determined by dot immunobinding assay. RESULTS: The infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P < 0.05). CONCLUSION: The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.

OBJECTIFS: Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée au 14 C, et des anticorps à H. pylori ont été détectés dans 9.183 échantillons de sérum par une méthode immuno-turbidimétrique au latex. La corrélation entre l'infection à H. pylori et les facteurs démographiques et économiques, le mode de vie et les antécédents médicaux des participants a été déterminée par un questionnaire. Les anticorps contre l'uréase de H. pylori, VacA et CagA dans le sérum ont été déterminés par un test dot par d'immuno-liaison. RÉSULTATS: Le taux d'infection à H. pylori était 53,0% et 90,1% des souches étaient du type I. Le taux d'infection à H. pylori est plus élevé chez les agriculteurs (OR = 1,34 ; IC95%: 1,19 à 1,50) et les personnes qui avaient un niveau d'instruction du premier cycle secondaire ou supérieur (OR = 1,10 ; IC95%: 01,06 à 01,15) et était plus faible chez les personnes âgées (OR = 0,86 ; IC95%: 0,83-0,90), les personnes à revenu élevé (OR = 0,93 ; IC95%: 0,90-0,95), les personnes ayant l'habitude de manger rapidement (OR = 0,93 ; IC9 %: 0,87-0,99) et les individus qui consommaient plus de fruits et de légumes (OR = 0,90 ; IC95%: 0,85-0,95). Les personnes ayant des antécédents de cholécystite/cholécystolithiase, d'hypertension et d'asthme avaient une corrélation négative avec l'infection à H. pylori (p <0,05 ). CONCLUSION: La prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

Diagnostic value of circulating lncRNAs as biomarkers of digestive system cancers: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors. METHODS: PubMed, Embase, Cochrane Library, and Web of science were searched for relevant articles that were published before April 2019, and a meta-analysis was conducted. RESULTS: 52 studies with 63 lncRNAs were discussed in the meta-analysis. The pooled sensitivity and specificity of diagnosis were 0.80 (95% CI: 0.79-0.81) and 0.76 (95% CI: 0.75-0.77), respectively. The pooled DOR (the diagnostic odds ratio) was 15.63 (95% CI: 12.77-19.12), and the overall AUC (the area under the curve) was 0.87. Besides, subgroup analyzes showed that the DOR and AUC of large sample sizes (>80), multiple lncRNAs, serum-based lncRNAs, and downregulation group were superior to those of small sample sizes (≤80), single lncRNA, plasma-based lncRNAs, and upregulation group, respectively. The current data also highlight that the diagnostic accuracy of circulating lncRNAs in the case of colorectal cancer was higher than gastric cancer, hepatocellular carcinoma, esophageal carcinoma, and pancreatic cancer. And there is no difference in the perspective of geographical regions. CONCLUSION: The circulating lncRNAs have high diagnostic value and accuracy in digestive system cancers and may serve as potential biomarkers.

The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways.

OBJECTIVE: Disulfiram is commonly used for alcohol abuse; however, recent studies have revealed its potential as an anti-cancer treatment. This study investigated the effects of disulfiram on gastric cancer and its underlying mechanisms of action. METHODS: The gastric cancer cell lines MKN-45 and SGC-7901 were used for all experiments. Cell proliferation was investigated using cell counting kit-8, cell migration and invasion were examined using Transwell assays, the proliferation and metastasis related proteins PCNA and MMP-2, respectively, were detected by ELISA. To explore the underlying molecular mechanisms, we also examined levels of proteins involved in the Wnt and NF-κB pathways by ELISA. RESULTS: Disulfiram significantly inhibited the proliferation, migration, and invasion of gastric cancer cells and decreased PCNA and MMP-2 levels. Additionally, disulfiram-treated MKN-45 and SGC-7901 cells showed reduced expression of Wnt, ß-catenin, and NF-κB. CONCLUSION: Disulfiram regulates the Wnt and NF-κB pathways, and thus could be a potential treatment for managing gastric cancer.

A novel tetrapeptide fluorescence sensor for early diagnosis of prostate cancer based on imaging Zn2+ in healthy versus cancerous cells.

Zinc as a biomarker can be used to diagnose the early stage prostate cancer, while ZIP1 protein, a zinc transporter is significantly down-regulated in prostate cancer cells. This behavior leads to the apparent alteration of the enrichment ability for zinc between early prostate cancer tissues and healthy tissues. This difference inspires us to develop a novel Zn2+ sensor that applies to the clinic diagnosis of early prostate cancer. We designed a tetrapeptide sensor H2L (Dansyl-Gly-Pro-Trp-Gly-NH2) according to the photo-induced electron transfer principle (PET), and it performed adequately in Zn2+ imaging of prostate cell lines. Based on the assessment of Zn2+ enrichment ability, there was distinctly lower Zn2+ concentrate in prostate cancer cell lines than healthy prostate epithelial cells. Furthermore, H2L displayed high sensitivity with a detection limit as low as 49.5 nM, and high specificity for Zn2+ detection. Also the low toxicity and the superior cell permeability of H2L made the imaging of Zn2+ ions detection safe and rapid. We expect that H2L to be a powerful tool for early diagnosis of prostate cancer and a good indicator for the precise resection of cancer tissue during surgery.

A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related mortality. Lack of prognostic indicators for patient survival hinders GC treatment and survival. METHODS AND RESULTS: Methylation profile data of patients with GC obtained from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylation sites as biomarkers for GC prognosis. The cohort was divided into training and validation sets. Univariate Cox, LASSO regression,and multivariate Cox analyses revealed a close correlation of a four-DNA methylation signature as a risk score model with the overall survival of patients with GC. The survival between high-risk and low-risk score patients with GC was significantly different. Analyses of receiver operating characteristics revealed a high prognostic accuracy of the four-DNA methylation signature in patients with GC. The subgroup analysis indicated that the accuracy included that for anatomical region, histologic grade, TNM stage, pathological stage, and sex. The GC prognosis based on the four-DNA methylation signature was more precise than that based on known biomarkers. CONCLUSIONS: The four-DNA methylation signature could serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of GC patients. This potential must be verified in a large-scale population cohort study and through basic research studies.

The Roles of microRNAs in Multidrug-Resistance Mechanisms in Gastric Cancer.

Multidrug resistance (MDR) is one of the most significant reasons for the chemotherapeutics failure in gastric cancer. Although accumulating investigations and researches have been made to elucidate the mechanisms of multidrug resistance, the detail is far from completely understood. The importance of microRNAs in cancer chemotherapeutic resistance has been demonstrated recently, which provides a new strategy to overcome multidrug resistance. The different mechanisms are related to the phenomena of MDR itself and the roles of miRNAs in these multi-mechanisms by which MDR is acquired. In turn, the aim of this review was to summarize recent publications of microRNAs in regulating MDR in gastric cancer, thereby potentially developing as targeted therapies. Further unraveling the roles of microRNAs in MDR mechanisms including the ATP-binding cassette (ABC) transporter family, autophagy induction, cancer stem cell regulation, hypoxia induction, DNA damage and repair, epigenetic regulation, and exosomes in gastric cancer will be helpful for us to win the battle against it.