Mounting evidence supports that fine particulate matter adversely impacts cardio-metabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia is not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of four repeated visits across four seasons since 2012. Daily ambient fine particulate matter (PM2.5) and personal black carbon (BC) levels ranged from 9.0 to 552.5 μg/m3 and 0.2 to 24.5 μg/m3, respectively, with extreme levels observed during January 2013. Cumulative PM2.5 exposure windows across the prior 1-7 days were significantly associated with systolic blood pressure (BP) elevations ranging from 2.0 (95% confidence interval 0.3-3.7) to 2.7 (0.6-4.8) mmHg per standard deviation increase [67.2 μg/m3]), while cumulative BC exposure during the previous 2-5 days were significantly associated with ranges in elevations in diastolic BP from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mmHg per standard deviation increase [3.6 μg/m3]). Both BC and PM2.5 were significantly associated with worsening insulin resistance (0.18 (0.01-0.36) and 0.22 (0.04-0.39) unit increase per standard deviation increase of personal-level BC, and 0.18 (0.02-0.34) and 0.22 (0.08-0.36) unit increase per standard deviation increase of ambient PM2.5 on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardio-metabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

Background and Purpose: The relationship between stroke and short-term temperature changes remains controversial. Therefore, we conducted a systematic review and meta-analysis to investigate the association between stroke and both high and low temperatures, and health assessment. Methods: We searched PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI) and Wanfang Data up to 14 September 2014. Study selection, quality assessment, and author-contractions were steps before data extraction. We converted all estimates effects into relative risk (RR) per 1 °C increase/decrease in temperature from 75th to 99th or 25th to 1st percentiles, then conducted meta-analyses to combine the ultimate RRs, and assessed health impact among the population. Results: 20 articles were included in the final analysis. The overall analysis showed a positive relationship between 1 °C change and the occurrence of major adverse cerebrovascular events (MACBE), 1.1% (95% confidence intervals (CI), 0.6 to 1.7) and 1.2% (95% CI, 0.8 to 1.6) increase for hot and cold effects separately. The same trends can be found in both effects of mortality and the cold effect for morbidity. Hot temperature acted as a protective factor of hemorrhage stroke (HS), −1.9% (95% CI, −2.8 to −0.9), however, it acted as a risk factor for ischemic stroke (IS), 1.2% (95% CI, 0.7 to 1.8). Conclusion: Short-term changes of both low and high temperature had statistically significant impacts on MACBE.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

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Exposure to PM2.5 had a statistically significant impact on BP and the magnitude of this effect may have substantially clinical implication.

Cannabidiol (CBD), an abundant nonpsychoactive constituent of marijuana, has been reported previously to protect against hepatic steatosis. In this study, we studied further the functions and mechanisms of CBD on liver inflammation induced by HFC diet. Mice feeding an HFC diet for 8 weeks were applied to test the protective effect of CBD on livers. RAW264.7 cells were incubated with LPS + ATP ± CBD to study the mechanisms of the effect of CBD against inflammasome activation. We found that CBD alleviated liver inflammation induced by HFC diet. CBD significantly inhibited the nuclear factor-κappa B (NF-κB) p65 nuclear translocation and the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome both in vivo and in vitro studies, which lead to the reduction of the expression of inflammation-related factors in our studies. In addition, Inhibitor of activation of NF-κB partly suppressed the NLRP3 inflammasome activation, while adding CBD further inhibited NF-κB activation and correspondingly suppressed the NLRP3 inflammasome activation in macrophages. In conclusion, the suppression of the activation of NLRP3 inflammasome through deactivation of NF-κB in macrophages by CBD might be one mechanism of its anti-inflammatory function in the liver. K E Y W O R D Scannabidiol, NF-κB, NLRP3 inflammasome, nonalcoholic steatohepatitis

The present study investigated the effects of microRNA-124-3p (miR-124-3p) expression on nasopharyngeal carcinoma (NPC) cells and its relevant mechanism. A total of 90 NPC tissues and 85 postnasal catarrh tissues were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect tissue samples and expression of miR-124-3p in CNE1, CNE2, SUNE1, H0NE1, 5-8F, 6-10B and C666-1 NPC cell line and immortalized nasopharyngeal epithelial cells line (NP69). Overexpressed miRNA-124-3p in CNE-2 was downregulated, and low-expressed miRNA‑124-3p in C666-1 was upregulated by liposome-mediated transfection. Cell Counting Kit-8 (CCK-8), flow cytometry, the scratch test, Transwell migration assay and Boyden chamber assays were used to detect cell proliferation, apoptosis, migration and invasion. The target gene of miRNA-124-3 calculated by bioinformatics was further determined using dual-luciferase system. Protein levels of the signal transducers and activators of transcription 3 (STAT3), phospho-STAT3 (p-STAT3), mouse anti-human cyclin D2 (CCND2) and matrix metalloproteinase-2 (MMP-2) were tested by western blotting. miRNA-124-3p expression in NPC was markedly downregulated compared to postnasal catarrh tissues (P<0.001); miRNA-124-3p expression showed close linkage with clinical stages, regional lymph node involvement and T stages (all P<0.001). miRNA-124-3p expression was lower in the 7 NPC cell lines than NP69 cells (all P<0.05). After upregulation of miR-124-3p, proliferation, apoptosis, migration and invasion of C666-1 cells were suppressed; while after downregulation of miR-124-3p, CNE2 cells were increased (all P<0.05). Expression of STAT3, p-STAT3, CCND2 and MMP-2 in C666-1 cells was decreased after transfection with miRNA-124-3p, and the above protein expression in CNE-2 cells was increased after inhibition of miRNA-124-3p (all P<0.05). To sum up, this study shows that miR-124-3p may negatively regulate the transcription of the STAT3 by interfering with its 3'UTR, and the degradation of STAT3 affects its downstream expression of such as p-STAT3, CCND2 and MMP-2, thereby promoting NPC cells apoptosis and inhibiting proliferation, migration and invasion of NPC cells.

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