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BackgroundDepression is a possible influence factor for the increased risk of incident atrial fibrillation (AF). Although several investigations have assessed their association, the results are still controversial. Therefore, we conducted a meta-analysis to evaluate the association between depression or using antidepressants and AF.MethodsWe systemically performed the literature retrieval from two electronic databases PubMed and EMBASE until March 2022 to extract relevant data. The hazard ratios (HRs) and odds ratios (OR) from included studies with 95% confidence intervals (CIs) were adjusted into the risk ratio (RR) and pooled by using the random-effects model.ResultsTotally 9 studies about the associations between depression or antidepressants and incident AF risk were included in this meta-analysis. Among them, 5 studies specifically analyzed the impact of antidepressants on the risk of AF. The outcomes of our analysis indicated that depression or depressive symptoms could increase AF risk (RR = 1.15, 95% CI, 1.03–1.27, P < 0.01). In addition, the use of antidepressants can also increase AF risk (RR = 1.16, 95% CI, 1.07–1.25, P < 0.001). These results remained unchanged when we remove the source of heterogeneity or adjust the analysis model into the fixed-effects model.ConclusionsBased on existing investigations, both depression and the use of antidepressants are closely related to the increase of incident AF risk.

Background Pegylated arginine deiminase (ADI-PEG20; pegargiminase) depletes arginine and improves survival outcomes for patients with argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM). Optimisation of ADI-PEG20-based therapy will require a deeper understanding of resistance mechanisms, including those mediated by the tumor microenvironment. Here, we sought to reverse translate increased tumoral macrophage infiltration in patients with ASS1-deficient MPM relapsing on pegargiminase therapy. Methods Macrophage-MPM tumor cell line (2591, MSTO, JU77) co-cultures treated with ADI-PEG20 were analyzed by flow cytometry. Microarray experiments of gene expression profiling were performed in ADI-PEG20-treated MPM tumor cells, and macrophage-relevant genetic “hits” were validated by qPCR, ELISA, and LC/MS. Cytokine and argininosuccinate analyses were performed using plasma from pegargiminase-treated patients with MPM. Results We identified that ASS1-expressing macrophages promoted viability of ADI-PEG20-treated ASS1-negative MPM cell lines. Microarray gene expression data revealed a dominant CXCR2-dependent chemotactic signature and co-expression of VEGF-A and IL-1α in ADI-PEG20-treated MPM cell lines. We confirmed that ASS1 in macrophages was IL-1α-inducible and that the argininosuccinate concentration doubled in the cell supernatant sufficient to restore MPM cell viability under co-culture conditions with ADI-PEG20. For further validation, we detected elevated plasma VEGF-A and CXCR2-dependent cytokines, and increased argininosuccinate in patients with MPM progressing on ADI-PEG20. Finally, liposomal clodronate depleted ADI-PEG20-driven macrophage infiltration and suppressed growth significantly in the MSTO xenograft murine model. Conclusions Collectively, our data indicate that ADI-PEG20-inducible cytokines orchestrate argininosuccinate fuelling of ASS1-deficient mesothelioma by macrophages. This novel stromal-mediated resistance pathway may be leveraged to optimize arginine deprivation therapy for mesothelioma and related arginine-dependent cancers.

Prostate cancer is the most common cancer and one of the leading causes of cancer mortality in males. Androgen-deprivation therapy (ADT) is an effective strategy to inhibit tumour growth at early stages. However, 10~50% of cases are estimated to progress to metastatic castration-resistant prostate cancer (mCRPC) which currently lacks effective treatments. Clinically, salvage treatment measures, such as endocrine therapy and chemotherapy, are mostly used for advanced prostate cancer, but their clinical outcomes are not ideal. When the existing clinical therapeutic methods can no longer inhibit the development of advanced prostate cancer, human adenovirus (HAdV)-based gene therapy and viral therapy present promising effects. Pre-clinical studies have shown its powerful oncolytic effect, and clinical studies are ongoing to further verify its effect and safety in prostate cancer treatment. Targeting the prostate by HAdV alone or in combination with radiotherapy and chemotherapy sheds light on patients with castration-resistant and advanced prostate cancer. This review summarizes the advantages of oncolytic virus-mediated cancer therapy, strategies of HAdV modification, and existing preclinical and clinical investigations of HAdV-mediated gene therapy to further evaluate the potential of oncolytic adenovirus in prostate cancer treatment.

BackgroundThe use of anticoagulants is an established strategy to prevent stroke, embolism, and cardiovascular mortality in patients with atrial fibrillation (AF), but its role in the prevention of incident diabetes is unclear. We aimed to investigate this question by using participant data from cohort studies.MethodsWe conducted a meta-analysis of participants to investigate the impact of direct oral anticoagulants (DOACs) on the risk of new-onset diabetes in AF patients. The collection of related data was performed in the PubMed and EMBASE databases until December 2021, including studies associated with evaluating the correlation between DOACs and incident diabetes. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted by the random-effects model with an inverse variance method.ResultsTwo cohort studies with a total of 24,434 patients were included in this study (warfarin: n = 6,906; DOACs: n = 17,528). Compared with warfarin, the use of DOACs could reduce the incident diabetic risk in AF patients (HR = 0.75, 95%CI: 0.68–0.82). Investigations about the effects of three major classes of DOACs showed that the individual use of dabigatran (HR = 0.76, 95%CI: 0.64–0.90), rivaroxaban (HR = 0.74, 95%CI: 0.64–0.87), apixaban (HR = 0.74, 95%CI: 0.60–0.92) and the combined use of rivaroxaban and apixaban (HR = 0.74, 95%CI: 0.66–0.84) could reduce the risk of new-onset diabetes compared with warfarin. This risk reduction effect could be observed in both male and female groups (HR = 0.73, 95%CI: 0.64–0.84, P < 0.00001; HR = 0.82, 95%CI: 0.82–0.99, P = 0.04).ConclusionsTreatment with DOACs compared with warfarin reduced the risk of new-onset diabetes in both male and female patients with AF.