Isotope dilution mass spectrometry is a reliable principle for small molecule analyte measurements.It is a precise,accurate method with very high specificity,which is very suitable for lowconcentration steroid hormones tests.The published reference methods are all based on this principle so far.In this paper,the applications of isotope dilution mass spectrometry in the determination of steroid hormones were reviewed.

This article summarized recent correlative literatures focusing on international standards on glycated hemoglobin.The basic concept,determination of glycated hemoglobin,the present review in laboratory measurement and metrological traceability was introduced.The international community has established reference system and metrological traceability to the International System of Units on HbA1c.Determination in glycated hemoglobin is still in incipient stage in our country.Both clinical laboratorians awareness and clinical determination need to be strengthened.

Objective To investigate preanalytical and intraindividual biological variations of 19 biochemistry analytes. Methods For the study of preanalytical variations, 10 consecutive blood specimens were taken from each of 21 individuals and the specimens were taken from different arms and with various evacuated blood tubes and venous occlusion durations and processed with different storages before and after centrifugal separation of serum. Another 3 aliquots of blood, each at an interval of 1 week, were taken from the individuals for the study of intraindividual biological variations. All the serum samples were analyzed in duplicate for 19 biochemistry analytes. Analysis of variance was performed on the results for the estimation of preanalytical and biological variations. Results Various preanalytical treatments or factors caused some systematic variations but random specimen errors were the main contributors of preanalytical variations. Chloride, sodium and calcium showed preanalytical variations of less than 1% and other analytes ranging from 1%-7%. Different analytes showed varied intraindividual biological variations. The least biological variations ( <2% ) were observed on chloride, sodium and calcium and the largest ( >20% ) on bilirubin,triglycerides, alanine aminotransferase and creafine kinase. Conclusions Preanalytical variations under laboratory settings in China and intraindividual biological variations in Chinese for 19 biochemistry analytes have been estimated. These data will be useful in the estimation of measurement uncertainty and the interpretation of clinical laboratory results.

To study the long-term toxicity of arginine esterase from Agkistrodon halys ussuriensis venom for the clinical application of arginine esterase in the future. Beagle dogs were used as experimental animals and were divided into control group, arginine esterase low dose group (0.06 u/kg), the middle dose group (0.18 u/kg) and high dose group (0.36 u/kg). Every group consisted of four dogs. The arginine esterase was given intravenously once a day for 180 days. Then three dogs in each group were sacrificed and the fourth one was fed without injecting arginine esterase for 15 days. The toxic reactions during treatment and recovery period were determined by evaluating and comparing the general criteria ( including locomotor activity, growth rate, appetite and death rate), clinical criteria (including blood test and urine test), pathological dissection and viscera coefficient of the treated animals and the control animals. There were no significant differences in general criteria. The clinical criteria of the treated animals were the same as those of the control animals except liver function. There were no significant differences in pathological dissection and viscera coefficient between the treated animals and the control animals except livers. The livers in high dose arginine esterase treated animals were swollen and vacuolated and there was significant difference in liver coefficient between them (P<0.05). The toxic symptom of liver disappeared after withdrawal of treatment. From these results, the non-toxic dose of arginine esterase for dogs was estimated to be 0.18 u/kg under the present study conditions and is about 15 times the clinical dosage for using the drug "Qingshuanmei" of which the main component is arginine esterase. The long-term toxicity test result indicates that the toxicity of pure arginine esterase is lower than that of "Qingshuanmei", suggesting that clinical use of the arginine esterase is safe.
Animals ; Anticoagulants ; toxicity ; Carboxylic Ester Hydrolases ; toxicity ; Crotalid Venoms ; enzymology ; toxicity ; Dogs ; Female ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Male

Objective To verify the trueness and assess the traceability of results from a routine chemistry system procedure for measurement of urea and ereatinine in serun.Methods Series of fresh frozen patieot sera,whose values of urea or creatinine were assigned by isotope dilution gas chromatography mass spectrometry (ID-GC/MS) or isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS),were chosen to be analyzed by a routine chemistry system.The measurement results of urea and creatinine by the routine chemistry system were used for linear regression analysis against the assigned values bv the ID-MS method to calculate the percentage deviation and assess the expected bias.Results For urea and creatinine,the linear regression equations between the routine chemistry system and ID-MS methods were Y =0.9890X + 0.0192 (R2 =0.9990) and Y =0.9815X-6.4794 (R2 =0.9989),and the average percentage bias were-0.41％ (P ＞0.05) and-4.20％ (P ＜ 0.05),respectively.The expected percentage bias at three medical decision levels were-0.46％,-0.83％ and-0.96％ for urea and -15.90％,-5.87％ and-2.95％ for creatinine.Conclusions The results of urea analyzed by the routine chemistry system were consistent with the ID-MS method,which suggested that the results of the routine system procedure could be traced to ID-GC/MS method.For creatinine,the bias between the results of routine procedures and the assigned values met the minimum acceptance criteria' derived from biologic deviations,which would be better if its specificity improved.

Objective To assess system deviation of HbA1c measurement in clinical laboratories in China by the national trueness verification project.Methods Bias assessing research.Two lots samples of human whole blood pools with different HbA1c concentration levels were prepared and sent to laboratories by dry ice package.Laboratories were asked to measure these samples in 5 repeats per set in three consecutive Wednesday separately,results were reported through Web-based software.Meanwhile the IFCC reference measurement procedure was applied to assign HbA1c reference values for the two lots samples.The following information or data were analyzed:measurement systems,intra-lab CVs and inter-lab robust CVs of all laboratories,inter-lab robust CVs and bias based on peer groups,et.al.The criterion of bias was set at ± 4.5％.Results 106 of 120 laboratories submitted results,including 88 using high performance liquid chromatography method,13 using immune turbidimetry method and 5 using enzymatic methods the intra-lab CVs of lot 201311 ranged from 0 to 4.6％,with median of 1.1％,while for lot 201312 the intra-lab precision ranged from CV0 to CV4.5％,with median of CV0.9％.The inter-lab robust CVs of 201311 and 201312 with single determinations were 5.6％ and 6.1％ and inter-lab robust CVs of 201311 and 201312 of each lab's average results were 5.9％ and 5.6％ respectively.The inter-lab CVs of group BIO-RAD,TOSOH,ARKRAY and PRIMUS at two level were less than 5％.For all laboratories,the percents of pass of 201311 and 201312 were 61/106(57.5％) and 56/106(52.8％) respectively.The pass ratio of each group on two lots were as follows:of group BIO-RAD were both 19/45 (42.2％),of group TOSOH were 85％ (17/20) and 75％ (15/20),of group ARKRAY were 71.4％ (10/14) and 50％ (7/14),of group PRIMUS were 6/8,5/8; of group immune turbidimetric method were both 46.2％ (6/13) and of group enzymatic were both 3/5.Conclusions There were improvement for the performance of trueness of HbA1c measurement in domestic laboratories,while some of them should be addressed.Academic,research institutions,EQA organizer,manufacturers and clinical laboratories should work together to achieve the standardization of HbA1c measurement.

Objective To evaluate the analytical performance of 7 homogeneous HDL-cholesterol reagents. Methods An altracentrifugation-HPLC method was used as the comparison method. Fourty fresh patient samples were analyzed by homogeneous methods and the comparison method. The homogeneous methods were all performed on a Hitachi 7170A chemistry analyzer according to the manufacturer's instructions, Precision, accuracy and total errors were analyzed. Results The homogeneous assays typically demonstrated within run coefficient variance(CV) of < 1%, and total CV of < 3%. Methods A, B and D showed average bias, bias at the medical decision points and total errors all within the NCEP performance criteria and method C and F unacceptable biases (-19.74% and 11.46%, respectively) and total errors according to the NCEP criteria. However, all the homogenous methods (A-F) had total errors of < 30%, as required by the US Clinical Laboratory Improvement Amendment (CLIA). Conclusions Homogeneous HDL-C assays have been shown to be reasonably precise, but discrepant results have been observed with some of the assays. Clinical laboratories should pay more attention on selecting and validating homogeneous HDL-C reagents.

Objective To develop a candidate reference method for the determination of sodium in serum by inductively coupled plasma mass spectrometry method (ICP-MS). Methods Aluminum, as internal standard of sodium, was added into serum samples and sodium standard solutions by gravimetric analysis. The samples were digested by HNO3 and diluted, and its 23Na/27Al isotope ratios were obtained by ICP-MS. The sodium concentrations were calculated with the standard curve method in serum. Results The analytical recoveries of sodium were 100.67% and 100.15% respectively, and the precisions were 0.08% and 0.04% respectively for 2 different serum samples. The results of measuring sodium in serum of Standard Reference Material (SRM) gave the coefficients of variation (CVs) of 0.18% and 0.22% for 2 levels of standard reference material(SRM) 909b and 0.41%, 0.41% and 0.66% for 3 levels of SRM 956b. The relative deviations between the results and median of the certified value were 0.17% and 0.14% for 909b and -0.09%, -1.05%, -0.48% for 956b respectively. Conclusions The ICP-MS and aluminum internal standard method is proved to be not only precise and accurate, but also quick and convenient for measuring sodium in serum. It is promising to be a candidate reference method for determination of sodium in serum.

Objective To analyze the incidence of BK virus (BKV) infection after kidney transplantation in our center and to evaluate the efficacy and safety of conversion treatment with Mizoribine (MZR) on BKV infection after kidney transplantation.Methods The information of recipients who received BK virus screening in hospital or outpatient during 2015-02 to 2016-12 in our center was retrospectively analyzed.The recipients positive for BKV were divided into experiment group (given conversion treatment with MZR) and control group (not given MZR conversion) according to the inclusion criteria.The negative rate of BKV,AR,hyperuricemia and the function of renal allograft during the conversion treatment with MZR were observed.Results 182 recipients accepted BKV screening during 2015-02 to 2016-12 and 68 cases were positive.The positive rate of BKV was 38.5 ％.The positive rate of peripheral blood specimens and midstream urine specimens was 7.1％ and 36.8％ respectively.Twelve recipients were positive for BKV in both peripheral blood specimens and midstream urine specimens.There were 27 recipients in experiment group and 36 cases in control group.Fourteen recipients positive for BKV became negative after MZR conversion in experiment group and the negative rate was up to 51.9％.The mean time of negative rate was 3.2 ± 2.7 (1-10) months after MZR conversion.During the conversion treatment with MZR,AR occurred in 1 case and was reversed by the impact therapy with Thymoglobulin in experiment group.The value of serum uric acid was maintained stable before and after MZR conversion under the action of uric-acidlowering drug.The renal function was kept stable in both experiment group and control group after renal transplantation.No deaths and renal allograft failure cases occurred in both groups during the research period.The 2-year survival rate for patients and kidneys was both 100％.Conclusion The incidence of BKV infection after kidney transplantation was high and the treatment scheme of MZR conversion was safe and effective.

Objective To summarize the puncture indications and the pathological type features of renal allografts biopsies in our center for evaluating its safety and diagnostic value .Methods The data of 773 percutaneous renal allograft biopsies in 629 kid‐ney transplants in the Pearl River Hospital of Southern Medical University from January 2005 to June 2014 were retrospectively an‐alyzed .Results The success rate of renal biopsy was 100% ,9 cases(1 .2% ) were complicated postoperative perirenal small hemato‐ma ,33 cases(4 .3% ) with gross hematuria and 1 case(0 .13% )with abdominal pain .Among the indications of 773 biopsies ,protein urine occured 205 cases(26 .5% ) of patient ,blood Cr increased in 187 cases(24 .2% )of patients ,protein urine simultaneously com‐plicating blood Cr increased ,in 313 cases of patients ,53 cases(6 .9% )had postoperative oliguria urinary ,and 15 cases(1 .9% )were get procedural biopsy .In the pathological types ,21 cases(2 .7% ) were normal ,179 cases (23 .2% ) were acute T cell‐mediated rejec‐tion after transplantation ,51 cases (6 .6% )were acute antibody‐mediated rejection ,205 cases (26 .5% ) were chronic T cell‐mediated rejection and 43 cases(5 .6% ) were chronic antibody‐mediated rejection;41 cases(5 .3% ) were drug toxicity ,29 cases(3 .7% ) were acute tubular necrosis(ATN) ,11 cases(1 .4% ) were relapsed or new nephropathy ;9 cases(1 .2% )were HBV related renal disease;39 cases (5 .0% ) were critical lesion and 145 cases(18 .8% )were others .Conclusion Rrenal allograft biopsy is safe ,it is important to the etiological diagnosis of renal disease after renal transplant ,which can guide the clinical treatment and improve the long term survival of renal graft and should be routinely carried out in clinic .