Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017

Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%).Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.Funding: As per sources of funding.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Clinical profile of ankylosing spondylitis patients in Togo

Aim of the workTo determine the clinical characteristics of ankylosing spondylitis (AS) in rheumatology wards in Togo. Patients and methods: The medical records of AS patients in four rheumatology wards in Togo were recorded from January 2000 to December 2019. Results: The study included 37 AS cases out of 35,304 rheumatic diseases patients’ files that were investigated over the preceding 20 years; accounting for 0.1% of hospital cases. Male predominance was noticed with a M:F ratio of 4.3. The mean age at disease onset was 29.6 ± 10.3 years and the mean duration of the symptoms was 9.5 ± 9.2 years. The clinical findings were dominated by spinal pain (91.9%). The main peripheral joints involvements were knees (48.6%) and ankles (35.1%) and the most frequent extra-articular features were ocular with conjunctivitis (13.5%) and uveitis (8.1%) respectively. Plain radiographs of the spine revealed syndesmophytes (45.9%) with bony ankylosis and bamboo spine (21.6%); and that of the pelvis showed sacroiliitis in 89.2%. The human leucocytic antigen (HLA B27) was positive in four cases. Non-steroidal anti-inflammatory drugs (NSAIDs) and sulfasalazine were the most commonly used drugs, respectively in 89.2% and 67.6% of patients. One patient was receiving biologic therapy. Conclusion: Ankylosing spondylitis is relatively rare in Togo. There is no particularity in the clinical features or imaging and laboratory findings. The diagnostic delay reflects the importance of the plain radiograph structural changes. NSAIDs and disease modifying anti-rheumatic drugs (DMARDs) are the cornerstone of the treatment due to their accessibility in Togo.     

Decreased expression levels of DAL-1 and TOB1 are associated with clinicopathological features and poor prognosis in gastric cancer

PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

Effects of newly introduced antidiabetic drugs on autophagy

Diabetes mellitus is a chronic metabolic disorder that has a complex molecular and cellular pathophysiology, resulting in its dynamic progression and that may show differing responses to therapy. The incidence of diabetes mellitus increases with age and requires additive therapeutic agents for its management. SGLT2i and DPP-4 inhibitors and GLP-1 receptor agonists (GLP-1RA) are newly introduced antidiabetic drugs that work through differing mechanisms; DPP-4 inhibitors maintain the endogenous level of GLP1; GLP-1RA result in pharmacological levels of GLP1, whilst SGLT2i act on the proximal tubules of the kidney. They have shown efficacy in the management of diabetes and in contrast to other antidiabetic drugs, do not inherently cause hypoglycemia in therapeutic doses. Autophagy as a highly conserved mechanism to maintain cell survival and homeostasis by degradation of damaged or aged organelles and components, and recognised to be increasingly important in diabetes. In the present review, we discuss the modulatory effects of these newly introduced antidiabetic drugs on the autophagy process.     

鞘磷脂类信号通路与动脉粥样硬化的研究进展

动脉粥样硬化是临床常见的冠心病和脑梗死等缺血性心脑血管疾病的主要病理基础,其病因复杂,发病机制尚未完全阐明。近年来,越来越多的研究显示鞘磷脂类信号通路可通过调节脂代谢、炎症和血管内皮功能等影响动脉粥样硬化的发生发展。文章综述了鞘磷脂类信号通路关键分子鞘磷脂、神经酰胺和1-磷酸鞘氨醇与动脉粥样硬化的关系,旨在为防治疾病提供新思路。