The efficacy and safety of osimertinib in treating nonsmall cell lung cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment. METHOD: The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS. RESULT: A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028). CONCLUSION: Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.

Vitamin D inhibits the Staphylococcal enterotoxin B-induced expression of tumor necrosis factor in microglial cells.

Microglial cells play a crucial role in inflammatory responses in neural tissue. Vitamin D (VitD3) deficiency is associated with the pathogenesis of inflammation. Staphylococcal enterotoxin B (SEB) is a superantigen and can initiate inflammation. This study tests a hypothesis that VitD3 deficiency upregulates the expression of tumor necrosis factor (TNF) in microglial cells. Microglial cells were isolated from the mouse brain. The microglial cells were cultured in the presence or absence of VitD3 or/and SEB. The expression of TNF in the microglial cells was assessed by RT-qPCR and Western blotting. We observed that SEB increased the expression of TNF in microglial cells. The presence of calcitriol (an active form of VitD3) inhibited the SEB-induced TNF production by microglial cells in a dose-dependent manner. Exposure to SEB increased the binding of vitamin D receptor (VDR) to the TNF promoter, which was inhibited by the presence of calcitriol with the mechanism being the formation of a complex of VDR and LITAF (a transcription factor of TNF) in microglial cells; the complex prevented the binding of LITAF to the promoter of the TNF gene. Exposure to calcitriol also increased the expression of IL-10 in microglial cells; the inhibition of SEB-induced TNF expression was partially due to the IL-10 induced by calcitriol (Heine G, Niesner U, Chang HD, teinmeyer A, Zügel U, Zuberbier T, et al. 1,25-dihydroxyvitamin D(3) promotes IL-10 production in human B cells. Eur J Immunol. 2008;38(8):2210-8). Hormonal vitamin D [calcitriol] can inhibit the SEB-induced TNF expression in microglial cells.

Micro RNA-550a interferes with vitamin D metabolism in peripheral B cells of patients with diabetes.

The pathogenesis of diabetes is to be further investigated. Vitamin D3 (VitD3) can improve diabetes. Micro RNAs (miR) are involved in regulating cell activities. This study tests a hypothesis that miR-550a interferes with the metabolism of VitD3 in peripheral B cells. In this study, blood samples were collected from patients with diabetes and healthy persons. The B cells were isolated from the blood samples to be treated with tumor necrosis factor (TNF)-α. The B cells were then collected and analyzed for the expression of miR-550a and cyp27b1. The results showed that B cells from healthy subjects were capable of converting VitD metabolite calcidiol to calcitriol, which was impaired in B cells collected from diabetic patients. The diabetic patients showed lower bone mineral density than that in healthy subject. The miR-550a was negatively correlated with bone mineral density and the Levels of cyp27b1 in peripheral B cells of patients with diabetes. In vitro study showed that TNF-α increased miR-550a expression and inhibited the expression of cyp27b1 in B cells. miR-550a mediated the effects of TNF-α on inducing chromatin remodeling at the cyp27b1 gene locus. In conclusion, miR-550a mediates the TNF-α-induced suppression of cyp27b1 expression in peripheral B cells of patients with diabetes, which can be blocked by inhibition of miR-550a.

Ankle-brachial index and brachial-ankle pulse wave velocity are associated with albuminuria in community-based Han Chinese.

BACKGROUND/OBJECTIVES: Our study aimed to explore whether the ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were associated with albuminuria in community-based Han Chinese. METHODS: Total 2127 subjects (860 men and 1267 women) aged 60 years and over were recruited in Beijing. Albuminuria was assessed by the urinary albumin-to-creatinine ratio (UACR) of ≥30 mg/g. BaPWV was divided by quartile. The logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (CIs) of ABI and baPWV with albuminuria. RESULTS: ABI was associated with albuminuria in the interaction model (OR 0.89, 95% CI 0.81-0.99 by every 0.1 unit increase of ABI), especially in hypertension (OR 0.82, 95% CI 0.73-0.92) and diabetes (OR 0.83, 95% CI 0.68-0.98) groups. BaPWV groups were also significantly associated with albuminuria, ORs of having albuminuria for baPWV quartile II, III, and IV were 1.02(0.65-1.52), 1.05(0.72-1.61), and 1.18(1.04-1.47) in the interaction model. For hypertension and diabetes patients, only the baPWV quartile IV group had higher OR. CONCLUSIONS: ABI and baPWV were associated with albuminuria after adjusting for other risk factors in Chinese community-based elderly Han population. The association of ABI with albuminuria was stronger in hypertension and diabetes patients.

The association of metabolic syndrome with left ventricular mass and geometry in community-based hypertensive patients among Han Chinese.

BACKGROUND: The association of metabolic syndrome (MS) with left ventricular (LV) hypertrophy is controversial. The objective of our study was to investigate the influence of MS on LV mass and geometry in community-based hypertensive patients among Han Chinese. MATERIALS AND METHODS: This study included 1733 metabolic syndrome patients according to the International Diabetes Federation (IDF) definition and 2373 non-MS hypertension patients. LV hypertrophy was diagnosed by the criteria of LV mass ≥49.2 g/m(2.7) for men and 46.7 g/m(2.7) for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LV hypertrophy and relative wall thickness. Logistic regression analysis was used to determine odds ratio (OR) and 95% confidence interval (CI) of MS for LV hypertrophy and LV geometry abnormality. RESULTS: The LV mass and LV mass index were higher in the MS group than in the non-MS group. In multiple adjusted models. LV mass index, LV mass, interventricular septum, and post wall were raised with the increased number of MS disorders. MS was associated with increased LV hypertrophy risk (unadjusted OR 1.38; 95% CI 1.21-1.57); age, sex, and blood pressure (BP; adjusted OR 1.39; 95% CI 1.22-1.59). MS was also associated with increased risk of eccentric hypertrophy in male and female patients. MS was only associated with increased risk of concentric hypertrophy in female patients; and MS was not associated with concentric remodeling. CONCLUSION: LV mass and LV mass index were associated with the increased number of MS disorders in the Chinese community-based hypertensive population. MS was not only associated with increased LV hypertrophy risk, but also associated with concentric and eccentric LV geometry abnormality, especially in females.

Measures of bioavailable serum sex hormone levels in aging Chinese by protein chip.

The purpose of this study was to develop a protein chip technique based on receptor binding assays to measure bioavailable serum sex hormone levels (BSSHL). 224 aging healthy Chinese were investigated to get the referenced values of BSSHL for the first time. In the assays recombined sex hormone receptor proteins were jointed to polysaccharide coated slides to make protein chip, and the dose-dependence curves of sex hormone on chip were prepared. The data showed that this method had good precision (CV < 16%) and accuracy (Bias < 10%), and the sensitivity could reach 1 pmol/L. From the results, BSSHL of men and women declined with aging, but no significant differences were observed. The BSSHL of aging men were higher than those of women. The bioavailable serum androgen level of men was 52-112 pmol/L, women's was 3-70 pmol/L and the whole group was 41.9-81.4 pmol/L. The bioavailable serum estrogen level of men was 0.8-3.0 pmol/L, women's was 1.2-2.5 pmol/L and the whole group was 0.6-2.64 pmol/L. Based on the assays, BSSHL measurement by protein chip can meet the needs of epidemiological studies in terms of speed, accuracy and sample volume required, and was helpful in quantitative assessment of aging people's health.