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  • 1
    In: BMJ Open, BMJ, Vol. 11, No. 10 ( 2021-10), p. e052274-
    Abstract: To analyse the relationship between serum uric acid (SUA), all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients to inform clinical practice and future research. Design A systematic review of observational studies. Data sources PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed, Chinese Science and Technology Journal Database (VIP) and Wan Fang databases were searched from their inception to January 2021 for cohort and case–control studies reporting SUA and mortality in patients with PD. Methods The Newcastle-Ottawa Quality Assessment Scale was used to appraise quality of cohort and case–control studies. Effect estimates were presented as HRs with 95% CIs in a meta-analysis using STATA V.16.0. Data not suitable for pooling were synthesised qualitatively. Results Fourteen cohort studies with 24 022 patients were included. No case–control studies were identified. For prospective cohort studies, pooled results for the highest SUA category were significantly greater than the lowest for all-cause (one study; 1278participants; HR 1.79; 95% CI 1.17 to 2.75) and CV mortality (one study; 1278 participants; HR 2.63; 1.62–4.27). An increase of 1 mg/dL in SUA level was associated with a 16% increased risk of all-cause mortality (one study; 1278 participants; HR 1.16; 1.03–1.32) and 34% increased CV mortality risk (one study; 1278 participants; HR 1.34; 1.16–1.55). For retrospective cohort studies, the highest SUA category did not demonstrate an elevated all-cause (five studies; 4570 participants; HR 1.09; 0.70–1.70) or CV mortality (three studies; 3748 participants; HR 1.00; 0.44–2.31) compared with the lowest SUA category. Additionally, there was no increase in all-cause (eight studies; 11 541 participants; HR 0.94; 0.88–1.02) or CV mortality (three studies; 7427 participants; HR 0.90; 0.76–1.06) for every 1 mg/dL increase in SUA level. Conclusions Results of prospective and retrospective cohort studies were inconsistent. Consequently, prospective, multicentre, long-term follow-up studies are required to confirm the relationship between SUA and mortality in patients with PD.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2599832-8
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  • 2
    In: Gut, BMJ, Vol. 69, No. 2 ( 2020-02), p. 343-354
    Abstract: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. Methods A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. Results Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. Conclusions The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
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