Overexpression of RAB31 in gastric cancer is associated with released exosomes and increased tumor cell invasion and metastasis.

BACKGROUND: Gastric cancer (GC) is one of most common cancers worldwide. Several studies have suggested that Rab31 functions as a membrane vesicle transport regulator; however, the mechanism by which RAB31 regulates exosome secretion and promotes metastasis remains to be clarified. METHODS: We examined the expression of RAB31 protein and mRNA in GC tissue samples via immunohistochemistry and reverse transcription-polymerase chain reaction assays, respectively. We elucidated the function of RAB31 in GC cells by constructing a cell model and a pulmonary metastatic model of GC with overexpression of RAB31. Protein mass spectrometry was used to identify the exosomal protein. RESULTS: RAB31 expression increased at both the protein and mRNA levels with the development of GC. Cells overexpressing RAB31 showed an enhanced ability to migrate in both the in vitro cell model and the pulmonary metastatic model of GC. Exosome nanoparticle tracking analysis and electron microscopy revealed that the both the number and size of the exosomes secreted by GC cells were reduced when RAB31 expression was depleted. Injection of exosomes derived from RAB31 overexpressing cells promoted pulmonary metastasis in vivo. Analysis of the exosomal proteins revealed that PSMA1 was overexpressed in GC tissue in accordance with RAB31 expression. PSMA1 overexpression was highly associated with poor prognosis of GC patients. CONCLUSION: Our findings revealed a key role for RAB31 in GC metastasis through regulation of exosome secretion.

Disease burden of primary gallbladder and biliary tract cancers associated with body mass index in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017.

OBJECTIVE: To investigate the incidence of primary gallbladder and biliary tract cancer, mortality and disability-adjusted life years (DALY) of the global burden from 1990 to 2017. METHODS: Data of 195 countries and territories from 1990 to 2017 were extracted from the Global Health Data Exchange. The age-standardized incidence rate (ASIR) and estimated annual percentage change (EAPC) were employed to quantify trends in the incidence of primary gallbladder and biliary tract cancer. The age-standardized death rate (ASDR), age-standardized DALY and their corresponding EAPC were used to evaluate mortality trends. RESULTS: The global incidence of primary gallbladder and biliary tract cancer rose by 75.9% from 119 900 cases in 1990 to 210 900 cases in 2017. The highest ASIR was observed in Chile (10.8 per 100 000 in 2017), followed by Japan and South Korea. Regions with the highest social development index (SDI) quintile also had the highest death cases associated with primary gallbladder and biliary tract cancer in 2017 (60 100, 95% UI 55 800-62 700). A high body mass index (BMI) was found to be closely related to age-standardized deaths and age-standardized DALY in most of the regions analyzed. CONCLUSIONS: Primary gallbladder and biliary tract cancer remains a serious threat to global public health, especially in high-SDI countries. The ASDR and age-standardized DALY decreased from 1990 to 2017. A high BMI may be associated with this cancer burden.

Impacts of psychological resilience on self-efficacy and quality of life in patients with diabetic foot ulcers: a prospective cross-sectional study.

BACKGROUND: Patients with diabetic foot ulcer (DFU) usually have a poor quality of life (QoL) and self-efficacy, which is affected by many risk factors. However, the role of psychological resilience in QoL and self-efficacy in DFU patients has remained unclear. METHODS: This prospective cross-sectional study was performed in a single center from January 2018 to February 2020. A total of 98 DFU patients were enrolled in this study. Some demographic and clinical data were prospectively collected from participants. The psychological resilience of participants was assessed by Connor-Davidson resilience scale (CD-RISC). Self-efficacy was also assessed using the diabetes management self-efficacy scale (DMSES) and QoL was assessed by the 36-item short-form (SF-36) health survey. Univariable and multivariable linear regression were used to analyze the risk factors of self-efficacy and QoL. Then, logistic regression was used to analyze the predictors of psychological resilience among the participants. RESULTS: A CD-RISC score of more than 85 points was defined as high psychological resilience in this study; there were 28 participants diagnosed with high psychological resilience and 70 patients with low psychological resilience. Those with high psychological resilience had significantly higher self-efficacy, general health, vitality, social functioning, role emotional, and mental health than those with low psychological resilience. According to multivariable linear regression, low psychological resilience and older age were identified as risk factors of self-efficacy. On the contrary, low psychological resilience, older age, lower perceived social support and higher level of glycated hemoglobin were identified as risk factors of QoL. Finally, males had lower psychological resilience than females and those receiving more social support had higher psychological resilience than participants receiving less social support. CONCLUSIONS: Some risk factors of QoL and self-efficacy were identified in this study and these results may provide some evidence for the improvement of QoL and self-efficacy in DFU patients. Being female and receiving higher social support were shown to have potential for improving psychological resilience in DFU patients.

IL28B genetic variations are associated with treatment response of patients with chronic hepatitis C in a Chinese Han population.

OBJECTIVES: This study aimed to investigate the association between interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) and sustained virological response (SVR) in Chinese Han patients with chronic hepatitis C (CHC) and to analyze the correlations between IL28B SNPs and their personal, virological and clinical characteristics. METHODS: Altogether 631 Chinese Han individuals, including 297 CHC patients treated with pegylated interferon α plus ribavirin, 14 spontaneous responders to hepatitis C virus (HCV) and 320 healthy controls were enrolled in the study. Two main SNPs of IL28B, rs12979860 and rs8099917, were genotyped using an SNaPshot Multiplex Assay. Associations between IL28B, treatment outcomes and the patients' characteristics were assessed by multivariate logistic regression. RESULTS: The proportion of individuals with the rs12979860 CC or rs8099917 TT genotype was similar in the healthy controls and the CHC patients, although all spontaneous responders presented with both genotypes. Patients with IL28B genotypes had a significantly high rate of rapid virological response (RVR) and SVR. Multivariate analysis revealed that the IL28B SNP rs12979860 CC genotype, being aged <40 years and having a non-genotype 1 (G1) were independent predictors for SVR. The rs12979860 CC genotype and rs8099917 TT genotypes were predictors for RVR. The rs12979860 CC and rs8099917 TT genotypes were more prevalent in patients with a non-G1 genotype than those with G1 genotype. CONCLUSIONS: IL28B rs12979860 CC genotype is a significant predictor for SVR and RVR in Chinese Han patients with CHC. Non-G1 HCV genotype is associated with favourable IL28B genotypes.

Resistin mediates the hepatic stellate cell phenotype.

AIM: To describe the role of resistin in liver fibrosis. METHODS: For the in vivo animal study, Sprague Dawley rats were subjected to bile duct ligation (BDL) for 4 wk. Rat liver, adipose tissue (epididymal fat) and serum were analyzed for resistin expression. For the in vitro experiment, rat primary hepatic stellate cells (HSCs) and Kupffer cells (KCs) were used. HSCs were exposed to recombinant resistin, and collagen  I, transforming growth factor ß1, α smooth muscle actin, tissue inhibitor of metalloproteinase 1 and connective tissue growth factor expression were analyzed. Resistin gene and protein expression was quantified as was the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8 and monocyte chemotactic protein-1 (MCP-1). The effects of resistin on HSC proliferation, migration and apoptosis were determined. The effects of resistin on KCs were also investigated. RESULTS: Following BDL, rat epididymal fat and serum rather than liver showed higher resistin expression compared to control rats. In liver, resistin was expressed in quiescent HSCs and KCs. Resistin treatment resulted in enhancement of TNFα, IL-6, IL-8 and MCP-1 gene expression and increased IL-6 and MCP-1 protein in HSCs. Resistin activated HSC phospho-MAPK/p38, and p38 inhibition diminished IL-6 and MCP-1 expression. Furthermore, resistin facilitated HSC proliferation and migration, but decreased apoptosis which was via an IL-6 and MCP-1 mechanism. Finally, resistin-induced transforming growth factor ß1 from KCs enhanced HSC collagen  I expression. CONCLUSION: Resistin directly and indirectly modulates HSC behavior towards a more pro-fibrogenic phenotype.

Distribution of hepatitis C virus genotypes in Chinese patients with chronic hepatitis C: correlation with patients' characteristics and clinical parameters.

OBJECTIVE: This study aimed to explore the most up-to-date distribution of hepatitis C virus (HCV) genotypes in China, especially the association between HCV genotypes and patients' characteristics and clinical parameters. METHODS: Sera from 483 HCV antibody-positive patients were genotyped using a HCV genotyping chip assay. The distribution of HCV genotypes, clinical parameters, modes of transmission and duration of infection were determined and the relationships among these parameters were analyzed. RESULTS: A total of 424 patients were successfully genotyped. HCV genotypes 1, 2, 3 and 6 were found with a constituent ratio of 72.1%, 12.3%, 10.6% and 5.0%, respectively, in which subtypes 1b (69.1%), 2a (11.6%) and 3a (7.5%) were prevalent. The mean age of patients with genotype 1 and 2 was significantly elder than those with genotype 3 and 6 (P < 0.05). The distribution of HCV genotypes in relation to the mode of HCV transmission was remarkable (P < 0.001). Transfusion of blood and blood products was the main mode of transmission. Most genotype 1 infection (53.1%) was found in the group with a duration of HCV infection of 10-20 years. Genotype 1b was independently associated with age (P = 0.001) and mode of HCV transmission (P = 0.007). CONCLUSIONS: The main HCV subtype was genotype 1b in Chinese patients. The prevalence of HCV genotypes was correlated with age and the mode of HCV transmission. Genotype 3a and 6 may become an increasing threat in the future.