OBJECTIVE:To excavate and evaluate the security alert signals of linezolid after marketing,and to provide refer-ence for rational drug use in clinic. METHODS:The reporting odds ratio(ROR)method was used to excavate the security alert signals from the adverse drug events(ADE)data in the OpenFDA platform of FDA during second quarter of 2004-2016. The low-er limit of 95%CI >1 was regarded as suggestive of ADE alert signal. RESULTS:A total of 6828534 reports were extracted, among which there were 7224 reports mainly induced by linezolid. Top 10 ADE reports were thrombocytopenia,drug interac-tion,thrombocytopenia,nausea,anaemia,serotonin syndrome,diarrhoea,pyrexia,drug ineffective,vomiting. After the detec-tion of top 200 ADE reports by ROR method,120 signals related to 18 system organ class(SOC)were identified. Top 5 ADE sig-nals in turn by SOC were medical examination,nervous system disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,cardiac disorders. The high risk signals with clinical reference value included 42 cases of optic neuropathy (ROR=56.33),350 cases of serotonin syndrome(ROR=52.86),162 cases of lactic acidosis(ROR=18.30),31 cases of endo-carditis (ROR=15.38),566 cases of thrombocytopenia (ROR=14.29),122 cases of bone marrow failure (ROR=14.20),261 cases of panhematopenia (ROR=11.92),86 cases of disseminated intravascular coagulation (ROR=10.91),58 cases of toxic epidermal necrolysis(ROR=9.06),etc. As for ADE reports,male was slightly higher than female,and the patients in age group of ≥45 reported evidently more compared to younger age group. CONCLUSIONS:By detecting and evaluating alert signals of li-nezolid through OpenFDA platform,we could effectively lay the foundation for further research of pharmacovigilance.

Objective To investigate the association between left ventricular diastolic function and arterial stiffness in patients with type 2 diabetes mellitus. Methods One hundred and two patients with type 2 diabetes( diabetic group),and 126 non-diabetic patients( control group) were selected from Jan. 2012 to Dec. 2013 in the Beijing Military General Hospital. The clinical features were recorded and free blood glucose (FBG ),blood lipids were measured. Cardio ankle vascular index( CAVI ) was measured by VS-1000 arteriosclerosis detector. Ultrasound heartbeat diagram was used to determine the left ventricular diastolic function indexes including the left atrial diameter(LAD),left ventricular early diastolicpeak velocity(E),left ventricular diastolic peak velocity(A),E/ A ratio and E peak deceleration time(EDT). Results The level of LAD,A, EDT,CAVI in diabetic patients were(39. 5 ± 5. 3)mm,(76. 6 ± 13. 5)cm/ s,(206. 6 ± 56. 3)ms,(9. 6 ± 1. 1)respectively,higher than those in control group((34. 4 ± 4. 2)mm,(71. 3 ± 13. 4)cm/ s,(185. 5 ± 34. 4)ms,(8. 5 ± 0. 9)). And E,E/ A level in diabetic group were(56. 6 ± 20. 4)cm/ s and(0. 73 ± 0. 21),significantly lower than the control group((67. 5 ± 16. 4)cm/ s and(0. 96 ± 0. 26)). The differences between the two groups were significant(P = 0. 001,0. 004,0. 002,0. 001,0. 001,0. 001). After adjusting the factors including body mass index and triglyceride,CAVI was negatively correlated with E/ A(r = - 0. 339,P< 0. 05))and positively correlated with EDT(r = 0. 314,P < 0. 05). Conclusion The diabetic patients with lower diastolic function and higher arterial stiffness,and the two factors are negatively correlation.

OBJECTIVE:To provide reference for vancomycin-induced neutropenia adverse reactions/adverse events in clinical diagnosis. METHODS:With a case of children with neutropenia treated by long-course and large-dose vancomycin,PubMed and CNKI were retrieved to collect related literature and the literature was analyzed. RESULTS:Neutropenia may be associated with vancomycin,based on causality criterion of adverse reaction in China. CONCLUSIONS:Vancomycin-induced neutropenia in chil-dren is most likely associated with prolonged exposure induced by infusion,vancomycin dosage should be reduced or stopped,and routine blood and plasma concentration should be closely monitored.

Objective To understand the characteristics of High-density lipoprotein cholesterol (HDL-C) distribution through analyzing serum HDL-C levels in healthy checkup subjects among local urbanese.Methods The checkup results of 36 454 cases were collected from 2009 to 2013 in Tangshan Gongren hospital (male:n =20 343,female:n =16 111).The cases with liver injury,abnormal blood glucoses,kidney injury and defined cerebrovascular diseases and metabolic disease were excluded.25 197 cases were analyzed as normal subjects including 11 114 males and 14 083 females.Kolmogorov-Smimov test,kruskal-wallis test,and Dunn multiple comparison test was performed using Bioconductor software 3.0.2 for testing normality distribution and comparing the difference of two or multiple groups,respectively.Results were analyzed statistically with R 3.0.2.Results The results showed that the average level (1.22-± 0.31) mmol/L of HDL-C among the overall population is lower than that of national average level(1.30 mmol/L).The median serum HDL-C level in female is higher than in male (1.27 and 1.08,x2 =2 606.34,P ＜0.01).HDL-C levels in male continuously increase from 1.06 mmol/L to 1.11 mmol/L with aging,especially in groups of over 50 years old than in groups of below 50 years old (x2 =75.19,P ＜ 0.01).Conclusions Based on 2007 guidance on prevention and treatment by national health bureau,this study showed that there are 29.69％ of the apparent healthy subjects,especially about 42.94％ of the male,representing low HDL-C level under the low limit of 1.04 mmol/L.These results showed that serum HDL-C level in Tangshan urbanese is lower than that of national average level,and HDL-C level in male is tended to increase with aging.

Objective:To analyze long-term therapeutic effect and safety of warfarin anticoagulant therapy of differ- ent intensity on aged patients with nonvalvular atrial fibrillation (NVAF). Methods:According to age,a total of 197 NVAF patients followed up for five years were divided into advanced aged group [n=65,≥80 (85.00±2.09) years],aged group [n=75,65-79 (76.50±2.27)years]and middle-aged group [n=57,<65 (57.40±2.18) years].All enrolled patients received long-term warfarin anticoagulant therapy,advanced aged group and aged group received low intensity anticoagulation,international normalized ratio (INR)was 1.6~2.5,while middle-aged group received standard intensity anticoagulation and the INR was 2.0~3.0. Thrombus events and incidence rates of hemorrhage etc.over five years were compared among three groups,and the safe dose range of warfarin was ex- plored.Results:During five-year follow-up,no acute cerebral infarction occurred in three groups.The bleeding and other adverse reaction among three groups were no significant difference (P>0.05).Compared with middle- aged group,there were significant reductions in warfarin dose [(3.29±0.49)mg/d vs.(2.95±0.38)mg/d,(2.85 ±0.49)mg/d],INR [(2.54±0.43)vs.(2.20±0.29),(2.16±0.32)]and CHA2DS2-VASc [(3.02±0.89) scores vs.(2.64±0.77)scores vs.(2.33±0.48)scores]in aged group and advanced aged group,P<0.01 all;but there were no significant difference between aged group and advanced aged group (P>0.05).There were no signif- icant difference in incidence rates of mild hemorrhage (21.1% vs.14.7% vs.24.6%)and severe hemorrhage (1.8% vs.1.3% vs.1.5%)among middle-aged group,aged group and advanced aged group,P>0.05 all.Conclu-sion:When INR is closely monitored,INR controlled within 1.6-2.5 warfarin anticoagulation is safe and effective for in aged patients with nonvalvular atrial fibrillation.

Objective To explore the factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia. Methods The general information, the biochemical test results, and plasma concentration of vancomycin were collected from 93 pediatric patients with severe gram-positive cocci pneumonia. The relative factors influencing trough concentration of vancomycin were analyzed retrospectively. Results With the dosage of 40-60 mg/(kg·d), serum trough concentration of vancomycin were between 10-20 mg/L in 26 patients, <10 mg/L in 54 cases, ≥20 mg/L in 13 cases. The ALT, AST, GFR, and γ-GT were significantly different among three groups (P<0.05); the 10-20 mg/L group had the highest levels of AST and γ-GT, the ≥20 mg/L group had the highest level of ALT and the lowest level of GFR. Multiple linear regression analysis showed that GFR was negatively linearly correlated with the serum trough concentration of vancomycin (R2=0.039, P<0.05). The median serum trough concentration of vancomycin in pediatric patients with GFR≥90, 60–90, 30–60 mL/(min·1.73m2) were 8.66, 18.21, 8.45 mg/L respectively, and the difference is statistically significant (P<0.05). Conclusions The serum trough concentration of vancomycin is negatively linearly correlated with GFR in pediatric patients with severe gram-positive cocci pneumonia. The patients with impaired renal function are easier to reach the target serum trough concentration of vancomycin. Clinical use of vancomycin should follow the low doses in the range the guideline recommended, and the serum trough concentration should be closely monitored.

Objective: To analyze long-term therapeutic effect and safety of warfarin anticoagulant therapy of different intensity on aged patients with nonvalvular atrial fibrillation (NVAF). Methods: According to age, a total of 197 NVAF patients followed up for five years were divided into advanced aged group [n=65，≥80(85±2.09)years], aged group [n=75, 65-79(76.5±2.27) years] and middle-aged group [n=57, ＜65(57.4±2.18)]. All enrolled patients received long-term warfarin anticoagulant therapy, advanced aged group and aged group received low intensity anticoagulation, international normalized ratio (INR) was 1.6~2.5, while middle-aged group received standard intensity anticoagulation and the INR was 2.0~3.0. Thrombus events and incidence rates of hemorrhage etc. over five years were compared among three groups, and the safe dose range of warfarin was explored. Results: During five-year follow-up, no acute cerebral infarction occurred in three groups. The bleeding and other adverse reaction among three groups were no significant difference（P＞0.05). Compared with middle-aged group, there were significant reductions in warfarin dose [(3.29±0.49) mg/d vs. (2.95±0.38) mg/d, (2.85±0.49) mg/d],INR [(2.54±0.43) vs. (2.20±0.29), (2.16±0.32)] and CHA2DS2-VASc [(3.02±0.89) score vs.( 2.64±0.77) score vs.( 2.33±0.48) score]in aged group and advanced aged group, P＜0.01 all; but there were no significant difference between aged group and advanced aged group (P>0.05). There were no significant difference in incidence rates of mild hemorrhage (21.1% vs. 14.7% vs. 24.6%) and severe hemorrhage (1.8% vs. 1.3% vs. 1.5%) among middle-aged group, aged group and advanced aged group, P>0.05 all. Conclusion: When INR is closely monitored, INR controlled within 1.6~2.5, warfarin anticoagulation is safe and effective in aged patients with nonvalvular atrial fibrillation.

Objective To explore the distribution characteristics of plasma renin concentration in patients with hypertension and the possibly methodological problems.Methods The subjects including 361 patients with hypertension[male: 184 cases, average age: (45.16±13.74)years old;female: 177 cases, average age: (51.04±12.68) years old]and 187 apparent healthy individuals[male: 92 cases, average age: (46.74±13.17)years old;female: 95 cases, average age: (47.33±13.18) years old]were recruited from Departments of Healthy Check-up and outpatients for hypertension in Tangshan Gongren Hospital. The plasma renin concentration was detected by chemiluminescence-Immunoassay.Results The plasma renin concentration shows log-transformed normal distribution both in healthy group and hypertension group. The range of plasma renin concentration in hypertension group is from 0.05 to 574.07 pg/ml, while that in apparent healthy group is from 3.24 to 120.40 pg/ml. The plasma renin concentration in both groups is higher in male than female (Hypertension t=2.19,P=0.029;Healthy people t=2.85,P=0.005). The average concentration of plasma renin in hypertension group is slightly higher, and the width of density distribution is larger in comparison with healthy group although there is no significant difference between them. However, the percentage of plasma renin abnormality was 26.59% (96/361) in hypertension group with 13.85%(50/361)of low renin subtype and 12.74%(46/361)of high renin subtype ConclusionsThe plasma renin concentration measured by Chemiluminescence-Immunoassay can be used as an effective tool for hypertension screening.

BACKGROUND:Human mesenchymal stem cells derived from Wharton's jelly(WJCs)display the characteristics of MSCs as defined by the International Society for Cellular Therapy.They can be differentiated into bone,cartilage,adipose,muscle,and neural cells.They can also support the expansion of other stem cells,be weli-tolerated by the immune system,and have the ability to home to tumors.OBJECTIVE:To investigate biological changes of WJCs and brain tumor stem cells(BTSCs)co-cultured in vitro.METHODS:WJCs cultured by situ cultivation and BTSCs used enzyme digestion way respectively,and gathering the 3rd passage of WJCs though subculturing as well as BTSCs.Two kinds of cells co-cultured in 24-well plates in serum-free medium (SFM)without any growth factor.3 and 7 days after co-cultured respectively,CD133 expression of suspension cells in the 24-well plates were identified by flow cytometry,and immunofluorescence was performed for Nestin and glial fibrillary acidic protein (GFAP)expression of adherent cells.Co-culture supernatant(CCS)re-suspended 3~(rd) passage of BTSCs and cultured into 96-well plates at day 3,which were used to determine the difference in cell growth curve in both groups using a microplate reader.RESULTS AND CONCLUSION:With the cocultivation days increasing,the phenomenon that tumor sphere cells began to be decomposed,adherent and differentiated observed by an inverted microscope.BTSCs in the co-cultured group expressed GFAP and Nestin when adherent and differentiated.The higher degree of malignant brain tumor tissue used in culturing BTSCs was,the higher expression of CD133 in BTSCs was.CD 133~+ in BTSCs declined when co-cultured with WJCs.Growth curve of brain tumor stem cells cultured in CCS compared with in SFM at day 3,which indicates that the proliferation of BTSCs inhibited obviously.Results indicated that CD 133~+ expression and proliferative capacity of BTSCs went down and BTSCs underwent differentiation during the co-culture in vitro.

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.