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Background: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure–efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. Methods: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. Results: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. Conclusion: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.

Background: Chuankezhi injection (CKZ) is a traditional Chinese medicine for the treatment of respiratory diseases and has been often used off-label as a nebulization therapy. However, little is known about the aerosolization performance and pulmonary fate of the inhaled CKZ. This study aimed to evaluate the aerodynamic characteristics of nebulizer generated aerosols and to compare the properties of pharmacokinetics, lung distribution and anti-inflammation effects of CKZ after intratracheal and intravenous administration. Methods: The nebulization performance was evaluated in vitro based on the aerodynamic particle size distribution and aerosol output. The concentrations of epimedins A, B, C and icariin, the main active ingredients of CKZ, in plasma, bronchoalveolar lavage fluids (BALF) and lung tissues were measured by LC-MS/MS analysis. The pulmonary anti-inflammatory efficacy were tested using LPS-induced pulmonary inflammation mice model as indicated by the total cells counts, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. Results: The aerosols of CKZ generated by a commercial nebulizer showed excellent aerodynamic properties and delivery output. Following intratracheal instillation of CKZ, epidemins A, B and C, and icariin, were absorbed into the bloodstream with the mean absorption time varying from 101.8 min to 271.8 min, and their absolute bioavailabilities ranging from 26.4 % to 104 %. The instillation of CKZ increased the lung to plasma concentration ratios by 25.5–718 folds compared to intravenous administration, leading to improved and prolonged local anti-inflammatory effects. Conclusion: Nebulization therapy of CKZ could be a promising alternative to the injectable counterpart.

This study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk. 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. 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; G1n: OR = 0.74, 95% CI : 0.63–0.87; G0n: OR = 1.12, 95% CI : 1.03–1.22). However, these associations were not found among women. 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. [ABSTRACT FROM AUTHOR]

The risk of dementia increases in patients with cognitive impairment. However, it is not clear what factors contribute to the onset of dementia in those with cognitive impairment. In this prospective cohort study, we will investigate the every-five-year incidence of cognitive impairment and prognostic factors for cognitive impairment. The Jidong cognitive impairment cohort was established from April 2012 to August 2015, during which we recruited 5854 healthy participants (55.1% male) older than 45 years (mean, 57 years). Participants received a health examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Cognitive impairment was evaluated using the Mini-Mental State Examination, and was defined as a Mini-Mental State Examination score of less than 24. Dementia was assessed using the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth edition), the International Working Group criteria, and the Mini-Mental State Examination score. The follow-up will continue until December 2024, during which a prognostic model will be constructed. The primary outcome is the presence/absence of dementia and the secondary outcome is quality of life. Baseline screening results showed the following: (1) Cognitive impairment was apparent in 320 participants (5.5%). These participants will be excluded from the Jidong cohort study, and the remaining participants will be followed up. (2) Of the 320 participants with cognitive impairment, there was a significantly higher prevalence of illiteracy than other education levels (35.9%, P < 0.05). Age, arterial hypertension, alcohol consumption, and passive smoking differed significantly between the cognitive impairment and healthy groups (P < 0.05). Multivariate logistic regression models showed that age (odds ratio [OR] = 1.059, 95% confidence interval [CI]: 1.044–1.074) and arterial hypertension (OR = 1.665, 95% CI: 1.143–2.427) were risk factors for mild cognitive impairment. With the increase of educational level (illiteracy, primary school, junior high school, high school, university, and above), cognitive impairment gradually decreased (OR < 1, P < 0.05). (3) This cohort study has initially screened for several risk factors for cognitive impairment at baseline, and subsequent prospective data will further describe, validate, and evaluate the effects of these risk factors on cognitive impairment and dementia. These results can provide clinical evidence for the early prevention of cognitive impairment and dementia. The study was approved by the Ethics Committee of Kailuan General Hospital of Tangshan City and the Medical Ethics Committee, Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation on July 12, 2013 (approval No. 2013 YILUNZI 1).

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.