The level and clinical significance of soluble ST2 in heart failure patients with atrial fibrillation / 中华检验医学杂志

Objective@#To determine the level of Soluble Suppression of Tumorigenicity-2 (sST2) in patients with heart failure(HF) and atrial fibrillation (AF), and to explore its diagnostic and prognostic value in patients with HF and AF.@*Methods@#A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital. And according to whether they had atrial fibrillation before admission, we categorized patients into: HF with sinus rhythm (HF-SR, n=90) and HF with AF(HF-AF, n=95). Meanwhile, 40 healthy controls were collected. Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared. Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA). Statistical methods such as nonparametric test and Spearman correlation analysis were used. The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups. And by using the COX risk model, Multi-factor COX analysis was used to analyze the prognosis of patients.@*Results@#Compared with healthy controls, the median (P25, P75) of Plasma sST2 levels in HF patients increased remarkably [32.93 (20.31-51.39) ng/mL vs 15.99(7.97-22.69) ng/mL, Z=-4.373, P<0.001]. Patients with HF-AF group had significantly higher test results [39.86 (27.20-59.21)] ng/mL than HF-SR group [24.74 (14.83-44.11)] ng/mL, Z=-6.783, P<0.001].In the HFmrEF and HFpEF subgroups, the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group (Z=-2.381, P=0.017; Z=-3.701, P<0.001).Spearman correlation analysis showed that, in HF-AF patients, plasma sST2 level was positively correlated with diastolic blood pressure, Hypertension, New York Association (NYHA) cardiac function classification Ⅲ to Ⅳ, white blood count(WBC), and the level of Alanine Aminotransferase (ALT), Υ-glutamine transaminase (Υ-GT), B-type natriuretic peptide (BNP) (r>0, P<0.05).Also, there is a negative correlation between sST2, left ventricular ejection fraction (LVEF) and estimated Glomerular Filtration Rate (eGFR) (r<0, P<0.05). At ROC analysis, sST2 showed predictive value in both HF-AF and HF-SR group, with an optimal cut-off value of 25.33 ng/mL(AUC 0.872, 95%CI: 0.805-0.935, P<0.001, sensitivity 81.1%, specificity 87.5%) and 23.34 ng/mL(AUC 0.665, 95%CI: 0.570-0.761, P<0.001, sensitivity 55.6%, specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699, respectively, and the AUC of sST2 was higher than that of BNP. Multi-factor COX analysis indicated that plasma sST2 level, BNP, NYHA cardiac function grading could be risk factors for cardiac events in HF patients. Plasma sST2, left atrial diameter (LA-D), and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF. The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL (χ2=7.625, P=0.006). The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL (χ2=4.287, P=0.038).@*Conclusions@#The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls. The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR. It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR, HF-AF than BNP. HF-AF Patients with plasma sST2 ≥ 39.86 ng/mL are prone to cardiovascular events.

Valuation and Uncertainty Evaluation of the Purity Determination of Aminopyrine by Different Methods / 中国药师

Objective:To study the valuation and uncertainty evaluation of the purity determination of aminopyrine by two different principle methods. Methods:According to Technical Norm of Primary Reference Material and Technical Norm of Measurement,HPLC and acid-base titration were selected for studying the valuation of the purity determination of aminopyrine, and the uncertainty evaluation of the two different principle methods was systematically evaluated. Results:By using the two different principle methods,the standard value and uncertainty of aminopyrine content was 99.66% ± 0.08%(k = 2,P = 0.95). Conclusion:The valuation and uncertainty evaluation of the purity determination of aminopyrine by using HPLC and acid-base titration are accurate and reliable,which can avoid the defects by using single analysis method,and is helpful to improve the level of quality evaluation and control of aminopyrine. The study provides scientific basis for the development of aminopyrine purity reference materials.

A potential role of plasma circulating microRNA-30d in acute coronary syndrome / 中华检验医学杂志

Objective To investigate the diagnosis and prognosis value of plasma microRNA-30d (miR-30d)in acute coronary syndrome(ACS)patients.Methods It retrospectively recruited 170 cases of ACS patients from TEDA International Cardiovascular Hospital between September 2011 to February 2012, including 70 STEMI(male 54,female 16), 52 NSTEMI(male 34,female 18),48 UAP(male 29,female 19).At the same time,41 healthy controls(male 24,female 17)were enrolled into the study.Plasma miR-30d levels were determined by real-time quantitative PCR.In order to evaluate the dynamic change of miR-30d and other cardiac biomarkers,20 plasma samples of AMI patients were collected at 0-3 h,4-6 h,7-9 h, 10-12 h after pectoralgia.ROC curves and Kaplan-Meier survival curve were used to investigate clinical value of miR-30d in ACS.Results At 0-3 h after pectoralgia, miR-30d were significant higher in STEMI 7.208(0.170-11 070.735)and NSTEMI 7.989(0.836-151.391)than the controls 1.561(0.044-17.520)（Z1＝-5.792,Z2 ＝-6.113,P＜0.001）, but there were no statistic differences between UAP 1.073 （0.051-11.095）patients and the controls（Z＝-0.325,P＝0.745）.In 20 AMI patients,miR-30d levels peaked at 4-6 h and then dropped following 7-9 h, both earlier than cTnI, and the variation tendency was positive correlated with cTnI（r＝0.402,P＜0.01）.At 0-3 h after pectoralgia, the AUC, sensitivity and specificity of miR-30d for differentiating AMI and UAP were 0.882（95％ CI:0.830-0.935）,0.795（95％CI:0.711-0.861）and 0.854（95％ CI:0.716-0.935）respectively.When combined miR-30d and cTnI, the diagnostic AUC and specificity were 0.937（95％ CI: 0.902-0.972）and 0.937（95％ CI:0.818-0.984）,both enhanced when compared with miR-30d or cTnI alone.Kaplan-Meier survival curves revealed that there were no significant correlations between the miR-30d levels and MACE in both 30 days and 12 months（χ$lt@span sup=1$gt@2$lt@/span$gt@＝0.506,P＝0.477 and χ$lt@span sup=1$gt@2$lt@/span$gt@＝0.002, P＝0.963 respectively）.Conclusion Plasma miR-30d may be used as a potential biomarker for early diagnosis, but not prognosis in ACS patients.

Similarity Evaluation of Dissolution Curves for Generic Preparation and Reference Preparation of Bisaco-dyl Enteric-coated Tablets / 中国药房

OBJECTIVE:To investigate the similarity of dissolution curves between generic preparations and reference prepara-tions of Bisacodyl enteric-coated tablets in various dissolution mediums,and to provide reference for improving production technolo-gy and internal quality of generic preparations. METHODS:Paddle method was adopted with rotation speed of 75 r/min. The disso-lution test was performed using 1000 mL pH 6.0 phosphate buffer solution,pH 6.8 phosphate buffer solution,water containing 2% sodium lauryl sulfate. HPLC method was used to determine average accumulative dissolution of main components from 3 kinds of generic preparations and reference preparations at different time points to draw out dissolution curves. Similarity factor(f2)meth-od was used to the similarity of dissolution curves. RESULTS:Dissolution curves of reference preparations were basically the same in 3 kinds of dissolution mediums. But the dissolution curve f2 of one generic preparation among 3 manufactures to dissolution curve of reference preparation were ≥50,namely the similarity. CONCLUSIONS:The quality of generic Bisacodyl enteric-coat-ed tablets produced by different manufacturers is obviously different;the generic preparations needs to be further improved in the production technology and internal quality. For domestic generic preparation,it is necessary to strengthen the real-time monitoring of its dissolution curve,to ensure the drug quality.

Determination of Content and Content Uniformity of Memantine Hydrochloride Dispersible Tablets by an Internal Standard Method of GC / 中国药师

Objective: To establish a GC method for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.Methods: The sample was dissolved in water, alkalified by sodium hydroxide solution and extracted by methylene chloride.An HP-5 gas chromatography column (50 m×0.32 mm, 1.05 μm) was used.The column temperature was programming increased, and the initial temperature maintained at 120 ℃ for 3 min, and then raised to 220 ℃ at a rate of 10℃·min-1 and maintained for 7 min.A hydrogen flame ionization detector (FID) was used and the split ratio was 1∶1.The inlet temperature was 230 ℃ and the detector temperature was 260 ℃.The injection volume was 1 μl and the carrier gas was nitrogen with high purity at a flow rate of 3.0 ml·min-1.Adamantane was used as the internal standard, and the internal standard method was used for the calculation.Results: The calibration curve was linear over the range of 0.05-1.0 mg·ml -1 (r=0.999 7).The detection limit and the limit of quantification was 1.1 ng and 3.3 ng, respectively.The average recovery was 100.2% (RSD =0.73%, n=9).Conclusion: The method has the advantages of simple operation, small extraction process toxicity, little environmental pollution, high accuracy and high specificity, and can be used for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.

Corin-serine protease and clinical applications in cardiovascular disease / 中华检验医学杂志

Corin is a newly identified membrance protease which responsible for converting pro-B-type natriuretic peptide to biologically active B-type natriuretic peptide.B-type natriuretic peptide play an important role in regulating blood pressure and cardiac function.It is a biological marker of heart failure.So Corin plays a role in reducing blood volume, blood pressure, regulating body fluid balance, and improving cardiac function.Corin may be used as a biomarker for heart failure or other cardiovascular disease.Recent studies have found that Corin is associated with the occurrence and development of cardiovascular diseases, such as heart failure and acute coronary syndrome.The article mainly expound the biological characteristics of Corin, testing methods and its clinical application in cardiovascular disease status.

Uncertainty Evaluation in the Determination of Sodium Valproate Tablets by GC with an Internal Standard Method / 中国药师

Objective:To evaluate the measurement uncertainty in the determination of sodium valproate tablets by GC with an in -ternal standard method , and determine the main sources of uncertainty .Methods:A GC internal standard method was selected to sys-tematically analyze the uncertainty in the determination of sodium valproate tablets , including the sample quantity , dilution ratio, purity and area repeatability of chromatographic peaks .Results: The expanded uncertainty of sodium valproate tablets was 2.7%, and the determination range of sodium valproate tablets was (96.3 ±2.7)%(k=2).Conclusion:The established GC internal standard meth-od for the uncertainty evaluation is reliable , which is helpful to improving the quality evaluation and control of sodium valproate tablets .

Simultaneous Residual Determination of Two Organic Solvents in Bisacodyl Raw Material by Head-space GC / 中国药房

OBJECTIVE:To establish a method for simultaneous residual determination of dichloromethane and ethyl acetate in bisacodyl raw material. METHODS:Head-space GC was performed on the capillary column of 6% cyanopropyl phenyl-94% di-methyl polysiloxane(DB-624)by temperature programming,the temperature of injector was 220 ℃,detector was flame ionization detector with temperature of 250 ℃,carrier gas was high purity nitrogen with the flow rate of 3.0 ml/min,split ration was 1∶10, headspace heating temperature was 70 ℃,equilibration time was 30 min,volume of headspace vial was 5 ml,and the injection volume was 1 ml. RESULTS:The linear range was 6-120μg/ml for dichloromethane(r=0.999 9)and 50-1 000μg/ml for ethyl ac-etate(r=0.999 9);the limit of quantitation was 0.2,1.7 μg,limit of detection was 0.06,0.5 μg;RSDs of precision,stability and reproducibility tests were no higher than 3%;recoveries were 100.30%-102.00%(RSD=0.63%,n=9) and 100.10 %-101.30%(RSD=0.44%,n=9). CONCLUSIONS:The method is simple and accurate,and can be used for the simultaneous residual deter-mination of dichloromethane and ethyl acetate in bisacodyl raw material.

Determination of Purity and Uncertainty Evaluation of Bisacodyl by Differential Scanning Calorimetry / 中国药房

OBJECTIVE:To establish the purity determination of bisacodyl by differential scanning calorimetry(DSC)and the valuation of uncertainty. METHODS:DSC was conducted to detect the purity of bisacodyl and determine the optimal testing condi-tions. According to related standards,indium enthalpy change values,measurement repeatability,weighing process,instrument tem-perature deviation and system software deviation were systematically analyzed. The results were verified by HPLC. RESULTS:When the fiducial probability P was 0.95,the standard value and uncertainty of content of bisacodyl was (99.88 ± 0.06)% mea-sured by DSC. Weighing process,instrument temperature deviation and system software deviation had great effects on the total un-certainty. The result of HPLC and DSC were the same. CONCLUSIONS:The established DSC can quickly and accurately determine the chemical purity of bisacodyl. The uncertainty evaluation is reliable. Regularly calibrated and verificated equipment and strict con-trol of the weighing process will help to improve the accuracy measured by DSC;and it provides a new analysis method for the de-termination of purity of bisacodyl.

Analytical performance of high-sensitivity cardiac troponin I detection by VITROS ECIQ with enhanced chemiluminescence method / 中华检验医学杂志

Objective To evaluate the performances of high-sensitivity cardiac troponin I ( cTnI ) on VITRO ECIQ with enhanced chemiluminescence method .Methods This verification study validated the limited of detection,function sensitivity,imprecision,linearity of the high-sensitivity cardic troponin used VITROS ECIQ according to the document EP-17A, EP-6A,EP-15A published by Clinical and Laboratory Standards Institute (CLSI) and determined 99th percentiles.All 652 patients with chest pain on immediate admission in TEDA International Cardiovascular Hospital during January to November 2013 were enrolled in this study.Including 323 cases of acute ST segment elevation myocardial infarction and non ST segment elevation myocardial infarction patients as the case group , exclude 329 cases of other diagnosis ,303 cases of apparent normal people as control group .The receiver operating characteristic curve was used to evaluated the sensitivity and the specificity of cTnI . Non-normal distribution of quantitative data were used nonparametric test Mann-Whitney U, With P was 1.73 % -2.33 %, reproducibility CV was 4.93% -9.96%.The imprecision were lower than that declared by assay producer.The linearity was 0.015 5-78.4 ng/ml(R2 =0.999 9); the 99th percentile reference value was 0.017 ng/ml.The area under the curve ( AUC) of cTnI was 0.986,95%CI 0.973 -0.994,with the cut-off value as 0.017 ng/ml, the diagnostic sensitivity and specificity in CIN were 90.09%and 99.34%.Compared between STEMI and NSTEMI groups after admission , the levels of cTnI had no significantly difference , Z were -0.485, P >0.05;compared between STEMI and control groups after admission, the levels of cTnI had significantly difference , Z were -19.567,P<0.001;compared between NSTEMI and control groups after admission , the levels of cTnI had significantly difference , Z were-14.598,P<0.001.Conclusions High-sensitivity cardiac troponin I detection by VITROS ECIQ with enhanced chemiluminescence method has good performances of sensitivity , linearity, specificity, which meet the clinical needs.

Association of LOX-1 and CX3CR1 with coronary artery stenosis disease and its outcomes / 中华检验医学杂志

Objective To explore the association of lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1),CX3C chemokine receptor 1 (CX3CR1) with coronary artery stenosis disease and its outcomes.Methods A case-control study was conducted.A total of 176 cases of coronary artery stenosis which were confirmed coronary artery stenosis ≥ 50％ by coronary angiography(CAG) were served as case group from department of cardiology of TEDA International Cardiovascular Hospital of Tianjin from May 2011 to April 2013.A total of 129 patients without coronary artery lesion by CAG from this hospital in the same period were served as control group,which has no history of heart disease,liver and kidney dysfuction,brain disease,hematological disease,other disorders that could bring out atherosclerosis and thrombosis.General information and laboratory parameters,LOX-1,CX3CR1,uric acid (UA) and creatinine (CREA) were measured in 2 groups.These parameters of each group were compared,the levels of LOX-1 and CX3CR1 in one-vessel stenosis were compared than that in multi-vessels stenosis in case group,the correlations between LOX-1,CX3CR1 and Gensini score and other variables were analyzed.Comparison of the levels of LOX-1 and CX3CR1 between major adverse cardiovascular events (MACEs) group and nonmajor adverse cardiovascular event (MACE) group was made during follow up 1.5 years.MACEs in patients with different levels of LOX-1 and CX3CR1 were compared during 1.5-year follow up.All of the data were analyzed by SPSS 16.0 software.The independent-samples T test,Mann-Whitney U test,Chi-square test,Spearman correlation,Binary Logistic Regression and Kaplan-Meier probability were adopted for data analysis.Results Comparison between case group and control group,LOX-1:3.72 (1.44,8.15) μg/L vs 0.75(0.50,1.19) μg/L,z =11.072,P ＜0.001 ;CX3CR1:(2.82 ± 1.85) μg/L vs (2.32 ±0.79) μg/L,t =2.021,P ＜ 0.05 ; UA:(351.34 ± 94.82) μmol/L vs (326.74 ± 79.51) μmol/L,t =2.094,P ＜ 0.05 ;CREA:(70.86 ± 20.94) μmol/L vs (65.55 ± 12.96) μmol/L,t =2.077,P ＜ 0.05.CX3CR1 level was significantly higher in patients with multi-vessels stenosis (2.84 ± 1.78) μg/L than that in one-vessel stenosis(2.48 ± 1.64) μg/L,there was significance in difference (t =2.207,P ＜ 0.05).There were no statistically significant correlation between LOX-1,CX3CR1 and Gensini score (R was 0.032,0.079 respectively,P＞ 0.05).LOX-1 was negatively related to left ventricular ejection fraction(LVEF) (R =-0.272,P ＜ 0.01),but positively related to left ventricular end-diastolic diameter (LVDD)(R =0.190,P＜0.05),positively related to UA (R =0.121,P ＜ 0.05).Comparison between MACE group and nonMACE group,LOX-1:7.38(4.97,11.88)μg/L vs 3.52(1.45,7.75) μg/L,z =2.762,P ＜0.01;CX3CRl:(4.02 ±2.90) μg/L vs (2.67 ± 1.48) μg/L,t =3.086,P ＜0.01.LOX-1 and TG were independent risk effects of coronary artery stenosis disease.MACEs were increased in patients with high levels of LOX-1 after PCI during following up 1.5 years (comparison between high-LOX-1 group and lowLOX-1 group,the probability of non-MACE was 87.1％ (115/132) vs 97.7％ (43/44),Log-ranK test,x2 =6.957,P ＜ 0.01).Conclusions LOX-1 and CX3CR1 may be involved in the process of coronary artery stenosis,and a high level of LOX-1 may be associated with left ventricular systolic dysfunction in patients with coronary artery stenosis.Elevated LOX-1 level are closely related to afterwards MACE incidence after PCI in patients with coronary artery stenosis.

The clinical significance of neutrophil gelatinase-associated lipocalin in early kidney injury after elective percutaneous coronary intervention / 中华检验医学杂志

Objective To explore the clinical application value of neutrophil gelatinase-associated lipocalin(NGAL)which were tested by immunity transmission turbidity in early kidney injury after elective percutaneous coronary intervention.Methods A case-control study was conducted.All 201 stable angina pectoris and acute coronary syndrome patients undergone percutaneous coronary intervention in TEDA International Cardiovascular Hospital,during April to August 2013,were enrolled in this study.Before and 2 h,4 h,8 h,24 h,48 h after the operation,the plasma creatinine of the patient samples were tested by enzymic method.Before and 2 h,4 h,8 h,24 h after the operation,the plasma NGAL was tested by immunity transmission turbidity method.Before and 8 h,24 h after the operation,the urinary NGAL was tested by immunoturdimetric method.The data were compared between contrast induced nephrpathy (CIN) and non-CIN groups.For normal distribution of quantitative data,t test were used and for non-normal distribution of quantitative data,nonparametric rank and inspection were used.Results CIN occurred in 8 of 201 enrolled patients,the incidence was 3.98％.Receiver operating characteristic curve (ROC) analysis confirmed the diagnostic accuracy of the plasma NGAL in CIN,and the area under the curve(AUC) of 2 h plasma NGAL was 0.928,95％ CI 0.800-0.985,with the cut-off value NGAL as 109 ng/ml,the diagnostic sensitivity and specificity for CIN were 87.5％ and 100％ ;the AUC of 8 h plasma NGAL was 0.945,95％ CI 0.824-0.992,with the cut-off value NGAL as 96 ng/ml,the diagnostic sensitivity and specificity for CIN were 87.5％ and 87.5％ ;the AUC of 8 h urinary NGAL was 0.969,95％ CI 0.859-0.999,with the cutoff value NGAL as 91 ng/ml,the diagnostic sensitivity and specificity for CIN were 87.5％ and 100％.Conclusions The change of plasma and urinary NGAL is earlier to that of serum creatinine for the early diagnosis of CIN.It can be used as the predictor of early renal damage after elective coronary artery interventional.

Postoperative prognosis of estimated glomerular filtration rate in coronary artery bypass graft surgery / 中华检验医学杂志

Objective To evaluate the postoperative prognosis of the modification of diet in renal disease formula (MDRD) in coronary artery bypass graft surgery (CABG) in hospital or 4 years after hospitalization. Methods Two hundred and seventy-two CABG patients were divided into 3 groups according to the levels of estimated glomerular filtration rate (eGFR) including 35 cases in eGFR < 60 ml/min group, 119 cases in 60 ≤ eGFR < 90 mL/min group and 118 cases in eGFR ≥90 ml/min group. The prognostic factors of CABG patients were analyzed by COX proportional hazards models. Kaplan-Meier survival analysis was used to compare survival curves among the three groups stratified by eGFR levels. The Log-rank statistic was used for comparing between groups. Results By multivariate COX regression adjustment for body mass index, smoking, hypertension, hyperlipaemia, diabetes mellitus, previous MI, perioperative PCI and etc. , the relative risk (RR) of the increasing age for cardiac events was 1.077(95% CI 1.002-1.158,P =0.044). RR of left ventricular ejection fraction (LVEF) was 0.005(95% CI 0.000-0.456,P =0.022). RR of eGFR was 0.968(95% CI 0.948-0.988,P =0.002). The survival rate in the first, second, third and fourth year were same in every group. The survival rate of group with eGFR < 60 ml/min, 60 ≤ eGFR < 90 ml/min and eGFR≥ 90 mL/min was 76.4%, 93.1%, and 96.6%. The survival rates among three groups were statistically significant. In the survival curve of 4 year follow-up after CABG, the survival rate of group with eGFR < 60 mL/min was lower than that of 60 ≤ eGFR < 90 ml/min group and eGFR ≥ 90 ml/min group. Conclusions The preoperative eGFR is an independent risk factor in evaluating cardiac events in hospital and after hospitalization. It has a higher prognosis value in patients undergoing CABG.

Optimization of the Determination Method of Terbinafine Hydrochloride by Non-aqueous Potentiometric Titration / 中国药房

OBJECTIVE: To improve the determination method of terbinafine hydrochloride by non-aqueous potentiometric titration.METHODS: Potentiometric titration was adopted to determine the content of terbinafine hydrochloride using glacial acetic acid as solvent,acetic anhydride instead of mercury acetate.Results of improved determination method were compared with that of primary method.RESULTS: One abrupt change was obtained in the titration curve.The repeatability precision RSD was lower than 0.15%.Results of improved determination method were compared with that of primary method with maximum deviation of 0.1%.CONCLUSION: Improved method not only discards mercuric salt but also obtain obvious abrupt change of titration curve.It is simple and rapid for the determination of terbinafine hydrochloride.