Dual-Recognition-Mediated Autocatalytic Amplification Assay for the Subpopulations of PD-L1 Positive Extracellular Vesicle.

The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.

Triglyceride-Glucose Index and the Risk of Stroke: A Systematic Review and Dose-Response Meta-Analysis.

Insulin resistance (IR) is an independent risk factor of cardiovascular disease. Recent research has proposed a new inexpensive and reliable indicator of IR: triglyceride glucose index (TyG index). We aim to evaluate the dose-response association between the TyG index and stroke through meta-analysis. Literature published from inception until October 2021 were searched in PubMed, Embase, Cochrane Library and Web of science. Cohort studies published in English and focusing on the association between the TyG index and stroke were included in our meta-analysis. I2 statistic and Chi-square were used to assess the heterogeneity. When I2≥30% or p≤0.10, the random-effect model was used to pool the effect; otherwise, we chose the fixed-effect model. Eleven cohort studies, including 5 721 077 subjects and 95 490 stroke patients, were included in our study. After pooling the effect adjusted by multiple confounders, we found that compared with the lowest baseline TyG index group, the highest one was independently associated with increased stroke risk (RR: 1.27; 95% CI, 1.24 to 1.29; I2=6%). Dose-response meta-analysis showed that the association between the two variables had a non-linear trend (p-nonlinearity<0.0001; p-heterogeneity=0.28). Subgroup analysis showed that the risk of ischemic stroke was positively correlated with TyG index (RR: 1.48; 95% CI, 1.34 to 1.62; I2=15%), while we did not observe this correlation in hemorrhagic stroke patients. In patients with type 2 diabetes and acute coronary syndrome, the TyG index was linearly correlated with incident strokes. In conclusion, elevated TyG index is the independent risk factor for incident strokes (especially ischemic stroke).

Low serum lipid levels, use of statin and cerebral microbleeds: A systematic review and meta-analysis.

INTRODUCTION: Previous studies have shown that low serum lipids and statins may be related to cerebral hemorrhage. We made the meta-analysis to evaluate the associations between serum lipid levels or statins treatment and cerebral microbleeds (CMBs) to identify whether the similar correlation also existed. METHOD: We comprehensively searched the Medline, Embase, Cochrane library, Web of Science, only included English journal articles, and systematically collected the observational studies and randomized controlled trials (RCTs) from September 1975 to August 2021. Random-effects model was used to pool data. Statistical heterogeneity was assessed by I2 statistic and chi-square. 11 items checklists recommended by the Agency for Healthcare Research and Quality (AHRQ), Newcastle-Ottawa Scale (NOS), and Cochrane Risk of Bias tool (ROB) were used to evaluate the methodological quality of cross-sectional studies, cohort studies and randomized controlled trial, respectively. RESULTS: Five cohort studies, two RCTs, and ten cross-sectional studies, including 16,637 subjects and 2663 CMBs patients, were included in our quantitative synthesis. Our study found that after adjusting the covariates, total cholesterol (TC) was significantly inversely correlated with the prevalent CMBs in any location, while total triglycerides (TG) and High-density lipoprotein (HDL) were significantly inversely associated with prevalent deep CMBs. Low-density lipoprotein (LDL) was negatively associated with incident CMBs after adjusted confounders. We did not found statistical differences between statin and CMBs after adjusted covariates. CONCLUSION: Serum major lipid (TC TG HDL LDL) levels may be inversely associated with CMBs. Currently, no sufficient evidence proves that statin therapy is the risk factor of CMBs.