The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events / 生物医学与环境科学（英文）

Objective@#To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.@*Methods@#A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.@*Results@#The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.@*Conclusion@#Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL / 基因组蛋白质组与生物信息学报·英文版

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells.</p><p><b>METHODS</b>Neuronal cells (primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin (Rap) or N-acetyl-L-cysteine (NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3'-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays.</p><p><b>RESULTS</b>Cd-induced activation of Akt/mTOR signaling, including Akt, mTOR, p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein (Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G).</p><p><b>CONCLUSION</b>Cd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.</p>

Analysis of blood lead level and its influencing factors of workers in one lead acid storage cell enterprise / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the blood lead level and its influencing factors of workers in one lead acid storage cell enterprise in Jiangsu Province.</p><p><b>METHODS</b>An occupational health field investigation was done to this storage cell enterprise at the end of June 2011 to measure the air lead fume (dust) concentration of workplaces. Health-care information of 1364 person-times from 2009 - 2011 was collected, including blood lead level, general state of health, life and health habit. One way ANOVA and ordinal multi-categorical logistic stepwise regression were used to analysis the influencing factors of blood lead level.</p><p><b>RESULTS</b>The lead fume concentration range was 0.008-0.354 mg/m(3) among 12 measuring points, which 7 places were unqualified, while the concentration range of lead dust was 0.023 - 2.432 mg/m(3), 24 out of 27 measuring places were unqualified, both the qualified rate were low. The blood lead concentration of objects was (259.54 ± 106.62) µg/L, among which 96 people (7.04%) who ≥ 400 µg/L should be identified as suspected "observation object", blood lead concentration ≥ 600 µg/L was not found. The blood lead concentration of male (279.76 ± 114.93 µg/L) was significantly higher than female (242.44 ± 95.86) µg/L (t = 6.441, P < 0.01). The proportion of ≥ 400 µg/L in male (11.04%, 69/625) was significantly higher than female (3.65%, 27/739) (χ(2) = 28.237, P < 0.01). The blood lead concentration of workers who exposed to lead fume or dust (265.93 ± 103.70) µg/L was significantly higher than those of not exposed to lead (205.30 ± 115.62) µg/L (t = -6.037, P < 0.01), the blood lead concentration of workers who exposed to lead dust was (267.38 ± 98.02) µg/L significantly higher than those of exposed to lead fume (260.81 ± 121.80) µg/L (t = -2.408, P < 0.05). The proportion of ≥ 400 µg/L in workers who exposed to lead fume (dust) (7.60%, 93/1223) was significantly higher than those of not exposed to lead (2.13%, 3/141) (χ(2) = 4.538, P < 0.05). Ordinal multi-categorical logistic stepwise regression found that the lead fume concentration ≥ 0.03 mg/m(3), lead dust concentration ≥ 0.05 mg/m(3) (OR = 1.59, 95%CI: 1.06 - 2.39), length of service ≥ 3 years (OR = 1.82, 95%CI: 1.12 - 2.98), smoking (OR = 2.06, 95%CI: 1.27 - 3.37) can increase the level of blood lead concentration.</p><p><b>CONCLUSIONS</b>Lead dust concentration of the enterprise exceeded the standard. Workers exposed to lead fume (dust) have more occupational health hazard of lead, of whom the blood lead concentration was high. Higher lead fume (dust) concentration in workplace, longer length of service, smoking were risk factors of high blood lead concentration.</p>