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Background This study aimed to summarize the previously published literature on the role of platelet-to-lymphocyte ratio (PLR) on overall survival (OS) in patients with gastric cancer. Methods We systematically searched PubMed, EmBase, and the Cochrane library to identify eligible studies to review. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity and subgroup analyses were performed, and publication bias was assessed. Results A total of 28 studies comprising 15,617 patients with gastric cancer were included in this meta-analysis. The pooled results indicated that elevated PLR was associated with poor OS (HR: 1.37; 95% CI: 1.24–1.51; P  < 0.001). A significant publication bias was observed (Egger test, P  = 0.036; Begg test, P  = 0.017). After adjusting for publication bias using the trim and fill method, an adjusted pooled HR of 1.19 (95% CI: 1.08–1.33; P  = 0.001) was observed. Subgroup analyses indicated an elevated PLR in retrospective studies. Studies conducted in Turkey, the UK, the USA, and Costa Rica; studies with a sample size of < 1000, with < 70% male patients, and with patients treated with chemotherapy; studies with PLR cutoff value of ≥200; and studies with lower quality as determined by the Newcastle-Ottawa Scale all showed greater harmful effects on OS than their corresponding subsets ( P  < 0.05). Conclusions An elevated PLR was associated with poor OS in patients with gastric cancer. These results might differ between studies due to differences in design, country of origin, sample size, sex proportion, treatment strategy, PLR cutoff value, and study quality.

Introduction: The pathological progression of non-alcoholic fatty liver disease (NAFLD) is driven by multiple factors, and non-alcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/ NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. Methods: A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. Data are available via Proteome X change with identifier PXD040233. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. Results: Bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and GSTA1). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP3A11 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). Discussion: These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.

Nasopharyngeal carcinoma (NPC) induced by latent infection with Epstein-Barr virus (EBV) remains the most common head and neck cancer in Southeast Asia, especially in the southern part of China. It is well known that persistent expression of two EBV latent membrane proteins (LMP1/LMP2A) plays a key role in nasopharyngeal carcinogenesis. Therefore, the therapeutic approach of targeting the LMP1/LMP2A protein and subsequently blocking the LMP1/LMP2A-mediated signalling pathway has been considered for treating patients with NPC. Recently, affibody molecules, a new class of small (~6.5 kDa) affinity proteins, have been confirmed to be powerful generalisable tools for developing imaging or therapeutic agents by targeting specific molecules. In this study, three EBV LMP2A N-terminal domain-binding affibody molecules (Z LMP2A-N 85, Z LMP2A-N 110 and Z LMP2A-N 252) were identified by screening a phage-displayed peptide library, and their high affinity and specificity for the EBV LMP2A N-terminal domain were confirmed by surface plasmon resonance (SPR), indirect immunofluorescence, co-immunoprecipitation and near-infrared small animal fluorescence imaging in vitro and in vivo. Moreover, affibody molecules targeting the EBV LMP2A N-terminal domain significantly reduced the viability of the EBV-positive cell lines C666-1, CNE-2Z and B95-8. Further investigations showed that affibody Z LMP2A-N 110 could inhibit the phosphorylation of AKT, GSK-3β and β-catenin signalling proteins, leading to suppression of β-catenin nuclear translocation and subsequent inhibition of c-Myc oncogene expression, which may be responsible for the reduced viability of NPC-derived cell lines. In conclusion, our findings provide a strong evidence that three novel EBV LMP2A N-terminal domain-binding affibody molecules have great potential for utilisation and development as agents for both molecular imaging and targeted therapy of EBV-related NPC.

Background This meta-analysis summarized the prognostic role of an elevated platelet count before treatment on survival outcomes in patients with cervical cancer. Methods The PubMed, Embase, and Cochrane library electronic databases were systematically searched for studies reporting the effect estimates with 95% confidence intervals (CIs) of pretreatment thrombocytosis on survival from the database inceptions to December 2018. The pooled hazard ratios (HRs) with 95% CIs for overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using random-effects models. Results Nineteen retrospective studies that recruited 6521 patients with cervical cancer were eligible for this study. The summary results indicated that an elevated platelet count was significantly associated with a poor OS (HR 1.50; 95% CI 1.19–1.88; P = 0.001), PFS (HR 1.33; 95% CI 1.07–1.64; P = 0.010), and RFS (HR 1.66; 95% CI 1.20–2.28; P = 0.002). Sensitivity analysis indicated that the pooled PFS was variable after sequential exclusion of individual studies. The predictive value of pretreatment thrombocytosis on OS differed according to the publication year ( P = 0.039), country ( P = 0.013), and sample size ( P = 0.029), and the role of pretreatment thrombocytosis on PFS could be affected by the study quality ( P = 0.046). Conclusion The findings of this study indicated that an elevated platelet count before treatment was associated with poor OS, PFS, and RFS. These results require further verification in large-scale prospective studies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Epstein-Barr virus (EBV) is widespread and is associated with nasopharyngeal carcinoma (NPC). Serological detection of EBV is commonly used for screening, diagnosis and epidemiological surveys of NPC. In the present study, a novel B cell multi-epitope peptide fusion protein (EBV-LMP2-3B), which is composed of three B cell linear epitopes (RIEDPPFNSLL, TLNLT and KSLSSTEFIPN) of EBV latent membrane protein 2 (LMP2), was expressed in a prokaryotic expression system and purified using Ni2+-nitrilotriacetate-Sepharose. The immunogenicity and binding specificity of EBV-LMP2-3B were evaluated on the basis of antibody responses in immunized BALB/c mice, western blotting and indirect immunofluorescence assay. Evaluation of EBV-LMP2-3B as a serological diagnostic reagent was performed using an indirect ELISA in 198 patients with NPC and 102 healthy adults. These results revealed that EBV-LMP2-3B was able to eliminate the high-titer serum antibody response in BALB/c mice. Western blot analysis and indirect immunofluorescence assay confirmed that the mouse immune sera recognized the native LMP2. Compared with healthy adults, patients with NPC demonstrated significantly greater reactivity to EBV-LMP2-3B (P<0.05). Furthermore, it was possible to effectively detect specific IgG in sera from patients with NPC, with a sensitivity of 91.91% and specificity of 93.14%, representing an improvement over the traditional viral capsid antigen-IgA-based detection method with 59.59% sensitivity and 75.49% specificity. In conclusion, the EBV-LMP2-3B protein may be used as a serological diagnostic reagent to screen for and diagnose NPC.