Xinqi Cheng

The high prevalence of hypovitaminosis D in China: a multicenter vitamin D status survey.

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25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays

Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy.

Prevalence and Clustering of Major Cardiovascular Risk Factors in China: A Recent Cross-Sectional Survey.

AbstractCardiovascular disease is the leading cause of death in the Chinese population. Although general prevalence estimates of cardiovascular risk factors (CVRFs) are available for Chinese adults, prevalence estimates covering all adult age groups by race/ethnicity have not been reported. The aim of this study is to estimate the current prevalence and clustering of major CVRFs in Chinese adults, including a plurality of ethnic minorities.A cross-sectional survey was conducted in a nationally representative sample of 23,010 adults aged 18 years and older from 2007 to 2011. Questionnaires and physical examinations were performed, and fasting blood was collected for laboratory measurements. The prevalence of traditional CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking, were determined.The prevalence of the major CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking were 24.3%, 4.3%, 49.3%, 32.0%, and 21.7%, respectively. These risk factors were significantly associated with sex, age, region, ethnicity, and education levels. Overall, 70.3%, 40.3%, and 16.7% of Chinese adults had ≥1, ≥2, or ≥3 CVRFs, respectively. Men, northern and rural residents were more likely to have clustered CVRFs compared with women, southern and urban residents, respectively. Compared with Han residents, Hui and Mongolian residents were more likely, and Tujia and Miao residents were less likely, to have ≥1, ≥2, or ≥3 risk factors. The prevalence of Chinese women having ≥1, ≥2, or ≥3 CVRFs decreased with increasing levels of education.The prevalence and clustering of CVRFs is still high in Chinese adults ≥18 years old, especially in men and in individuals living in the northern and rural areas. Of note, there are differences in cardiovascular risk among different ethnic groups. Therefore, targeted and enhanced intervention measures are required to reduce the risk of cardiovascular disease and the corresponding economic burden of disease in China.

Improved glomerular filtration rate estimation using New equations combined with standardized cystatin C and creatinine in Chinese adult chronic kidney disease patients

OBJECTIVES The newly developed glomerular filtration rate (GFR)-estimating equations developed by the CKD-EPI Collaboration and Feng et al. (2013) that are based on standardized serum cystatin C (ScysC), combined/not combined with serum creatinine (Scr), require further validation in China. We compared the performance of four new equations (CKD-EPIcys, CKD-EPIcr-cys, Fengcys, and Fengcr-cys equations) with the CKD-EPI creatinine equation (CKD-EPIcr) in adult Chinese chronic kidney disease (CKD) patients to clarify their clinical application. DESIGN AND METHODS GFR was measured using the dual plasma sampling (99m)Tc-DTPA method (mGFR) in 252 adult CKD patients enrolled from four centres. Scr and ScysC were measured by standardized assays in a central laboratory. Each equations performance was assessed using bias, precision, accuracy, agreement, and correct classification of the CKD stage. RESULTS The measured GFR was 46 [25-83] mL/min per 1.73 m(2). The CKD-EPIcys, CKD-EPIcr-cys and Fengcys equations provided significantly higher accuracy (P15: 38.9%, 39.7%, and 38.9%) than the CKD-EPIcr equation (29.8%). The CKD-EPIcr-cys and Fengcr-cys equations presented higher precision (IQR of the difference, 16.4 and 17.3 mL/min per 1.73 m(2), respectively) and narrower acceptable limits in Bland-Altman analysis (56.6 and 50.8 mL/min per 1.73 m(2), respectively) than single marker-based equations. The CKD-EPIcr-cys equation achieved the highest overall correct proportion (61.5%) in classification of CKD stages. CONCLUSIONS Combining ScysC and Scr measurements for GFR estimation improves diagnostic performance. The Scr-ScysC equation showed better performance than equations based on either marker alone. The CKD-EPIcr-cys equation showed the best performance for GFR estimation in Chinese adult CKD patients.

Nationwide Multicenter Reference Interval Study for 28 Common Biochemical Analytes in China

AbstractA nationwide multicenter study was conducted in the China to explore sources of variation of reference values and establish reference intervals for 28 common biochemical analytes, as a part of the International Federation of Clinical Chemistry and Laboratory Medicine, Committee on Reference Intervals and Decision Limits (IFCC/C-RIDL) global study on reference values.A total of 3148 apparently healthy volunteers were recruited in 6 cities covering a wide area in China. Blood samples were tested in 2 central laboratories using Beckman Coulter AU5800 chemistry analyzers. Certified reference materials and value-assigned serum panel were used for standardization of test results. Multiple regression analysis was performed to explore sources of variation. Need for partition of reference intervals was evaluated based on 3-level nested ANOVA. After secondary exclusion using the latent abnormal values exclusion method, reference intervals were derived by a parametric method using the modified Box–Cox formula.Test results of 20 analytes were made traceable to reference measurement procedures. By the ANOVA, significant sex-related and age-related differences were observed in 12 and 12 analytes, respectively. A small regional difference was observed in the results for albumin, glucose, and sodium. Multiple regression analysis revealed BMI-related changes in results of 9 analytes for man and 6 for woman. Reference intervals of 28 analytes were computed with 17 analytes partitioned by sex and/or age.In conclusion, reference intervals of 28 common chemistry analytes applicable to Chinese Han population were established by use of the latest methodology. Reference intervals of 20 analytes traceable to reference measurement procedures can be used as common reference intervals, whereas others can be used as the assay system-specific reference intervals in China.

Hyperuricemia and clustering of cardiovascular risk factors in the Chinese adult population

Hyperuricemia is common in China and the relevance of hyperuricemia and cardiovascular disease (CVD) risk has been highlighted, but to date there has been rarely nation-wide study in China. Here, we aim to estimate the current prevalence of hyperuricemia and evaluate the associations between hyperuricemia and cardiovascular risk factors (CRFs) clustering in a large sample of China adults including a plurality of ethnic minorities. Generally, a nationally representative sample of 22983 adults aged ≥18 years was recruited from 2007 to 2011. Questionnaire data and information on anthropometric characteristics, and laboratory measurements were collected. We define hyperuricemia as SUA ≥416 mmol/L for men and SUA ≥357 mmol/L for women. We found that the prevalence of hyperuricemia was 13.0% (18.5% in men and 8.0% in women). To our estimation, hyperuricemic subjects had higher prevalence rates of CRFs clustering than non-hyperuricemic subjects. Furthermore, there was a dose-response association between the number of CVD risk factors clustering and hyperuricemia. Our study revealed a high prevalence of hyperuricemia and CVD risk factors clustering among Chinese adults, and hyperuricemia was significantly associated with coexistence of more CVD risk factors. Therefore, guidance and effective lifestyle intervention are required to prevent hyperuricemia and CVD risk factors in China.

Strong Negative Interference by Calcium Dobesilate in Sarcosine Oxidase Assays for Serum Creatinine Involving the Trinder Reaction

Abstract The vasoprotective drug calcium dobesilate is known to interfere with creatinine (Cr) quantifications in sarcosine oxidase enzymatic (SOE) assays. The aim of this study was to investigate this interference in 8 different commercially available assays and to determine its clinical significance. In in vitro experiments, interference was evaluated at 3 Cr levels. For this, Cr was quantified by SOE assays in pooled serum supplemented with calcium dobesilate at final concentrations of 0, 2, 4, 8, 16, 32, and 64 &mgr;g/mL. Percent bias was calculated relative to the drug-free specimen. For in vivo analyses, changes in serum concentrations of Cr, cystatin C (CysC; a renal function marker), and calcium dobesilate were monitored in healthy participants of group I before and after oral calcium dobesilate administration. In addition, variations in interference were also examined among different SOE assays using serum obtained from healthy participants of group II. Lastly, Cr levels from the 10 patients treated with calcium dobesilate were measured using 4 SOE assays and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for comparison. Our in vitro analyses indicated that the presence of 8 &mgr;g/mL calcium dobesilate resulted in a −4.4% to −36.3% reduction in Cr serum concentration compared to drug-free serum for 8 SOE assays examined. In vivo, Cr values decreased relative to the baseline level with increasing drug concentration, with the lowest Cr levels obtained at 2 or 3 hours after drug administration in participants of group I. The observed Cr concentrations for participants in group II were reduced by −28.5% to −3.1% and −60.5% to −11.6% at 0 and 2 hours after administration related to baseline levels. The Cr values of 10 patients measured by Roche, Beckman, Maker, and Merit Choice SOE assays showed an average deviation of −20.0%, −22.4%, −14.2%, and −29.6%, respectively, compared to values obtained by LC-IDMS/MS. These results revealed a clinically significant negative interference with calcium dobesilate in all sarcosine oxidase-based Cr assays, but the degree of interference varied greatly among the assays examined. Thus, extra care should be taken in evaluating Cr quantification obtained by SOE assays in patients undergoing calcium dobesilate therapy.

Validation and comparison of a rapid liquid chromatography tandem mass spectrometry method for serum 25OHD with the efficiency of separating 3-epi 25OHD3.

OBJECTIVES To develop a rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method with ability to separate 3-epi 25OHD3 (EPI-LC-MS/MS) from 25OHD3, and evaluate the effects of 3-epi 25OHD3 on routine LC-MS/MS that cannot separate 3-epi 25OHD3 (NEPI-LC-MS/MS). DESIGN AND METHODS Performance of the newly built EPI-LC-MS/MS was validated, and 982 samples were analyzed and compared by the two methods. RESULTS Both methods showed a linearity coefficient correlation exceeding 0.999 in the 6.25-500nmol/L range for 25OHD2 and 25OHD3. Moreover, they showed a between run coefficient variation (CV) and total CV of < 5% for 25OHD2 and 25OHD3. The results of the accuracy test showed that the bias was below 6.19% in the absence of 3-epi 25OHD3. Comparison of the 25OHD results obtained by the two methods for 982 patients (age 1-100years) revealed excellent clinical agreement (Cohens kappa=0.875) and correlation (R2=0.973). Among the 982patients, only 73patients had 3-epi 25OHD3 (>6.25nmol/L); out of these 73patients, the 3-epi 25OHD3 level in 58patients was between 6.25 and 12.5nmol/L. In patients with <375nmol/L 25OHD (25OHD2+25OHD3), only 8 had 3-epi 25OHD3 levels exceeding 12.5nmol/L (range: 13.3 - 27.5nmol/L). Among samples containing 3-epi 25OHD3, only three were separated into different 25OHD-deficiency groups using the above methods. CONCLUSION A rapid and precise EPI-LC-MS/MS method for measuring 25OHD with efficient separation of 3-epi 25OHD3 was developed. Our results showed that 3-epi 25OHD3 had little effect on the routinely used NEPI-LC-MS/MS.

Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population.

Objective Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE) polymorphisms and hyperuricemia in a Chinese population. Methods A total of 770 subjects (356 hyperuricemic cases and 414 normouricemic controls) were recruited from the Ningxia Hui Autonomous Region, China. A physical examination was performed and fasting blood was collected for biochemical tests, including determination of the levels of serum lipid, creatinine, and uric acid. Multi-ARMS PCR was applied to determine the APOE genotypes, followed by an investigation of the distribution of APOE genotypes and alleles frequencies in the controls and cases. Results The frequencies of the APOE-ε2ε3 genotype (17.70% vs. 10.39%, P = 0.003) and the APOE-ε2 allele (10.53% vs. 5.80%, P = 0.001) were significantly higher in the hyperuricemic group than in the normouricemic group. Furthermore, male cases were more likely to have the APOE-ε2ε3 genotype and APOE-ε2 allele, compared with male controls. In both Han and Hui subjects, cases were more likely to have the APOE-ε2ε3 genotype and the APOE-ε2 allele compared with controls. Furthermore, multivariate logistic regression showed that carriers of the APOE-ε2ε3 genotype (P = 0.001, OR = 2.194) and the ε2 allele (P = 0.001, OR = 2.099) were significantly more likely to experience hyperuricemia than carriers of the ε3/ε3 genotype and the ε3 allele after adjustment for sex, body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), creatinine (Cr) and fasting blood glucose(FBG). Conclusions The APOE-ε2ε3 genotype and the APOE-ε2 allele are associated with serum uric acid levels in Chinese subjects, indicating that individuals carrying the APOE-ε2 allele have a higher risk of hyperuricemia than non-carriers.

A Multicenter Reference Intervals Study for Specific Proteins in China

AbstractA multicenter study conducted in healthy population of 6 cities from the 4 corners and central China for 7 serum-specific proteins to identify the sources of variation and establish the reference intervals on 2 automation platforms.A total of 3148 subjects aged 19 to 64 years old were enrolled in this study to ensure at least 120 participants in each 10-year age group and each city. The majority of samples were transported to central laboratory and measured on both Beckman AU5800 and Immage 800 analytical systems. Three-level nested ANOVA, multiple regression analysis, and the scatter plot were used to explore the variations from sex, age, region, BMI, cigarette smoking, and so on. The latent abnormal value exclusion (LAVE) method was applied at the time of computing RIs as a method for secondary exclusion.Regionality was not observed in any of the immunoassay in China. Variations for sex were significant for IgM among the immune analytes. For CRP and hsCRP results with turbidimetry method (Beckman Coulter AU5800) were lower than the nephelometry method (Beckman Immage). The LAVE method did not affect the RIs computed for the majority of analytes except C4, CRP, and hsCRP. In the scatter plot at the age of 45 years old C3, C4, and IgM reached an inflection point, accordingly RIs were separated by the age group.With the lack of regional differences and the well-standardized status of test results, the RIs of C3, IgG, IgA, IgM derived from this nationwide study can be used for the entire Chinese population. C4, CRP, and hsCRP were affected by different platforms and gender was a significant source of variation for IgM, so they had separated RIs.