Inhalable spray-dried porous microparticles containing dehydroandrographolide succinate phospholipid complex capable of improving and prolonging pulmonary anti-inflammatory efficacy in mice.

Due to the unique physiological barriers within the lungs, there are considerable challenges in developing drug delivery systems enabling prolonged drug exposure to respiratory epithelial cells. Here, we report a PulmoSphere-based dry powder technology that incorporates a drug-phospholipid complex to promote intracellular retention of dehydroandrographolide succinate (DAS) in respiratory epithelial cells following pulmonary delivery. The DAS-phospholipid complex has the ability to self-assemble into nanoparticles. After spray-drying to produce PulmoSphere microparticles loaded with the drug-phospholipid complex, the rehydrated microparticles discharge the phospholipid complex without altering its physicochemical properties. The microparticles containing the DAS-phospholipid complex exhibit remarkable aerodynamic properties with a fine particle fraction of ∼ 60% and a mass median aerodynamic diameter of ∼ 2.3 µm. These properties facilitate deposition in the alveolar region. In vitro cell culture and lung tissue explants experiments reveal that the drug-phospholipid complex prolongs intracellular residence time and lung tissue retention due to the slow intracellular disassociation of drug from the complex. Once deposited in the lungs, the DAS-phospholipid complex loaded microparticles increase and extend drug exposure to the lung tissues and the immune cells compared to the free DAS counterpart. The improved drug exposure to airway epithelial cells, but not immune cells, is related to a prolonged duration of pulmonary anti-inflammation at decreased doses in a mouse model of acute lung injury induced by lipopolysaccharide. Overall, the phospholipid complex loaded microparticles present a promising approach for improved treatment of respiratory diseases, e.g. pneumonia and acute respiratory distress syndrome.

A Nested Case-Control Study to Explore the Association between Immunoglobulin G N-glycans and Ischemic Stroke / 生物医学与环境科学（英文）

OBJECTIVE@#This study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk.@*METHODS@#A nested case-control study was conducted in the China suboptimal health cohort study, which recruited 4,313 individuals in 2013-2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. IgG N-glycans in baseline plasma samples were analyzed.@*RESULTS@#A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks (GPs) were separated from IgG N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference, obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men (FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio ( OR) = 0.92, 95% confidence interval ( CI): 0.87-0.97; G1 n: OR = 0.74, 95% CI: 0.63-0.87; G0 n: OR = 1.12, 95% CI: 1.03-1.22). However, these associations were not found among women.@*CONCLUSION@#This study validated that altered IgG N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.

[An epidemiological survey of malignant tumors among fluoride-exposed workers in aluminum industry].

OBJECTIVE: To investigate the incidence of malignant tumors among fluoride-exposed workers in aluminum industry. METHODS: Sampling points were set in the working positions at different radii around an workshop for treating the waste gas from aluminum electrolysis, and the concentrations of fluoride ions, aluminum, and benzo[a]pyrene (B[a]P) in air were measured by electrode method, atomic absorption spectrophotometry, and high performance liquid chromatography, respectively. The incidence of tumors among the workers in the aluminum plant from 1995 to 2009 was investigated by questionnaires and medical records and then statistically analyzed. RESULTS: There was a negative correlation between the concentrations of fluoride and aluminum and the radius around the fluoride source at each sampling point. B[a]P was not detected at each sampling point. The crude incidence rate of tumors among factory workers was 117.95/100 000 (standardized rate = 58.81/100 000); the standardized incidence rate of tumors was higher in female workers than in male workers (male-to-female ratio = 1:2.64). The peak age of onset of tumors was 40 ∼ 49 years. The most and second most common tumors were liver cancer and lung cancer in male workers and breast cancer and lung cancer in female workers. Compared with the unexposed population in the city where the aluminum plant was located, the female fluoride-exposed workers had an increased tumor incidence, 2.14 times that of the city's average level, and the fluoride-exposed workers had a younger age of onset of tumors and approximately the same types of tumors. CONCLUSION: Fluoride exposure may lead to an increasing trend in tumor incidence among female workers in aluminum industry.