1.Data Mining and Analysis of Safety Signals of Osimertinib after Marketing
China Pharmacy 2019;30(12):1692-1696
OBJECTIVE: To mine the signals of osimertinib adverse drug event (ADEs) and to provide reference for clinical drug safety. METHODS: By reporting odd ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms, data mining and signal detection were carried out on osimertinib-related ADEs reports with case number ≥3 reported by American Adverse Event Reporting System (FAERS) from Nov. 2015 to Jun. 2018. RESULTS & CONCLUSIONS: A total of 2 044 osimertinib-related ADEs were found, among which the female (1 285 cases) was more than the male (615 cases), mainly aged 45-64 years (228 cases), 65-74 years (241 cases), ≥75 years (248 cases); most of reporters were physicians (887 cases). A total of 63 and 57 osimertinib ADEs signals were mined by ROR and BCPNN methods, and the latter signals overlapped with the former. The obtained signals included skin toxicity (dermatitis acneiform, rash, dry skin, onychoclasis, nail disorder, paronychia), gastrointestinal tract reaction (decreased appetite, diarrhea, stomatitis), respiratory diseases (interstitial pneumonia, pneumonia), hematological diseases (platelet count decreased, white blood cell count decreased, neutrophil count decreased), vascular events (pulmonary embolism, deep vein thrombosis), electrocardiogram QT prolonged (RORs were 2.04-56.70, ICs were 0.97-4.43), all of which had been recorded in drug instructions; obtained signals also included new suspicious signals not indicated in the drug instructions, such as liver damage, cerebral infarction, hyponatremia, atrial fibrillation, renal impairment, dehydration, dysgeusia, and so on (RORs were 2.06-161.74, ICs were 1.00-4.58). In clinical use of osimertinib, besides paying close attention to known safety problems such as nail toxicity of finger (toe) and rash, interstitial pneumonia, electrocardiogram QT prolonged, we should also be alert to the occurrence of potential ADEs such as liver damage to ensure drug safety.
2.Construction of targeted umbilical cord derived mesenchymal stem cells and their distribution in the mouse spleen
Liwei QIN ; Ningkun ZHAMG ; Ping LU ; Xiujun PENG ; Guiqin WANG ; Yuan GAO ; Liqun CAO ; Bei CUI ; Jianwei GUO
Chinese Journal of Comparative Medicine 2015;(6):32-35,83
Objective To construct lentiviral vectors containing peptide P1-GFP fusion genes.Umbilical cord derived mesenchymal stem cells were infected with lentivirus carrying peptide P1 and GFP fusion genes.To inject the targeted umbilical cord derived mesenchymal stem cells into mice and to detect GFP expression in the spleen.Methods Umbilical cord derived mesenchymal stem cells were cultured with adhered tissues of umbilical cord smaller than 1 mm3 . Lentiviral vector containing P1-GFP fusion genes with engineering technology was constructed and infected the umbilical cord derive mesenchymal stem cells.Targeted umbilical cord derived mesenchymal stem cells were intravenously injected in the mouse tail vein and after 18 hours GFP expression was detected with immunohistochamical staining of the spleen tissues.Results Harvested umbilical cord derived mesenchymal stem cells grew well in culture medium. Green fluorescence on umbilical cord derived mesenchymal stem cells were observed under fluorescence microscope at 18 hours after infected with lentivirus.Green fluorescence intensity of umbilical cord derived mesenchymal stem cells was increasing over time and reached a peak at 72 hours.Umbilical cord derived mesenchymal stem cells highly expressed CD105 (90.0%)/CD44 (98%) and CD73 (85.0%)/CD90 (98.5%) molecules.GFP expression was detected in the spleen after intravenous injection of targeted umbilical cord derived mesenchymal stem cells in the mice 18 hours later.GFP expressing cells intimately contacted with lymphocytes.Conclusions Targeted umbilical cord derived mesenchymal stem cells contain P1-GFP fusion genes are constructed.Targeted umbilical cord derived mesenchymal stem cells can be targeted to mouse spleen and intimately contact with lymphocytes after intravenous injection.Our results lay the groundwork for further studies.

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