PurposeThis study aimed i) to identify the best cutoff points of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) that predict sarcopenia and ii) to illustrate the association between sarcopenia risk and NLR or PLR in renal cell carcinoma (RCC) patients undergoing laparoscopic partial or radical nephrectomy.MethodsA total of 343 RCC patients who underwent laparoscopic partial or radical nephrectomy between 2014 and 2019 were enrolled in our study. Sarcopenia was assessed by lumbar skeletal muscle index (SMI). Receiver operating characteristic (ROC) curve was used to identify the best cutoff point of NLR or PLR to predict sarcopenia risk. Univariate and multivariate logistic regression and dose–response analysis curves of restricted cubic spline function were conducted to assess the relationship between sarcopenia and NLR or PLR.ResultsThe best cutoff points of NLR >2.88 or PLR >135.63 were confirmed by the ROC curve to predict sarcopenia risk. Dose–response curves showed that the risk of sarcopenia increased with raising NLR and PLR. Patients with NLR >2.88 or PLR >135.63 had a higher sarcopenia risk than those in the NLR ≤2.8 or PLR ≤135.63 group, respectively. By adjusting for all variables, we found that patients with NLR >2.88 and PLR >135.63 had 149% and 85% higher risk to develop sarcopenia, respectively, than those with NLR ≤2.8 (aOR = 2.49; 95% CI = 1.56–3.98; p < 0.001) or PLR ≤135.63 (aOR = 1.85; 95% CI = 1.16–2.95; p = 0.010).ConclusionIn RCC patients receiving laparoscopic partial or radical nephrectomy, NLR and PLR, which were biomarkers of systemic inflammation, were associated with sarcopenia risk.
BackgroundTumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines.MethodsTissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid–liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment.ResultsYY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors.ConclusionsPhase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer–promoter interactions, thereby increasing PCa progression.
To better evaluate and enhance the performance and benefit of sustainable stormwater management (SSWM) in developing countries, this study proposes a comprehensive evaluation framework based on thorough literature review. This framework re-classifies evaluation goals and indicators into four aspects—stormwater system, integrated management, social engagement, and urban development. The purpose of this review is to provide a guideline for decision makers to choose appropriate goals and indicators according to different regional context. Meanwhile, a structured procedure for comprehensive evaluation of SSWM is proposed to guide a well-organised decision-making process. Furthermore, pros and cons of eight decision support tools, as well as their functional focus, are compared, aiming to provide references for SSWM in developing countries. Outcomes presented in this review are expected to support decision makers in the process of screening optimal SSWM strategies and monitoring SSWM projects.
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