Jianhua Han

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.

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.

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.

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.

A multicenter study on PIVKA reference interval of healthy population and establishment of PIVKA cutoff value for hepatocellular carcinoma diagnosis in China

The aim of this study was to investigate the reference interval of protein‐induced vitamin K absence or antagonist‐II (PIVKA‐II) in China population and to evaluate its medical decision level for hepatocellular carcinoma (HCC) diagnosis.

Validation of a simple inductively coupled plasma mass spectrometry method for detecting urine and serum iodine and evaluation of iodine status of pregnant women in Beijing

Abstract Rapid and simple method for serum and urine iodine is necessary for iodine-related diseases. This study aimed to establish and validate a simple and rapid method for quantification of iodine in human urine and serum using inductively coupled plasma mass spectrometry (ICP-MS). Generally, samples were diluted using water with 1.5% isopropanol and 7 mmol hydrous ammonium before analysis by the ICP-MS. Performance of the method was validated, and the urine and serum iodine levels of 72 pregnant women were analyzed. Results showed that the lower limit of detection of the ICP-MS method was 0.87 µg/L. No significant memory effects were observed. Recovery in both serum and urine was approximately 100%. Compared with NIST SRM3668, bias was <1%, exhibiting good accuracy. The inter-run coefficients of variation (CVs) for serum and urine iodine were 2.8–3.5% and 3.5–6.7%, respectively, and total CVs for serum and urine iodine were 3.2–3.7% and 3.9–6.7%, respectively. Comparison of the iodine results obtained by the ICP-MS method and the conventional S–K method revealed excellent correlation (r = 0.984, mean bias = –1.7%). The median urine iodine of pregnant women (125.5 μg/L) was lower than that of WHO criteria for iodine deficiency (median urinary iodine <150 μg/L) while 55.6% of the individuals with urine iodine level less than 150 μg/L. The median serum iodine level of the pregnant women was 69.0 μg/L. In conclusion, a rapid and simple ICP-MS method for urine and serum iodine measurements has been established and validated, and the pregnant women in Beijing may still suffer from insufficient iodine intake. AbbreviationsCV coefficients of variationHPLC high-performance liquid chromatographyICP-MS inductively coupled plasma mass spectrometryKED kinetic energy discriminationKI potassium iodideLOD limit of detectionS–K Sandell–Kolthoff reactionPUMCH Peking Union Medical College Hospital

CCCTC-binding factor inhibits breast cancer cell proliferation and metastasis via inactivation of the nuclear factor-kappaB pathway

CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues. In addition, CTCF expression correlated significantly with cancer stage (P = 0.043) and pathological differentiation (P = 0.029). Furthermore, CTCF overexpression resulted in the inhibition of proliferation, migration, and invasion, while CTCF knockdown induced these processes in breast cancer cells. Transcriptome analysis and further experimental confirmation in MDA-MD-231 cells revealed that forced overexpression of CTCF might attenuate the DNA-binding ability of nuclear factor-kappaB (NF-κB) p65 subunit and inhibit activation of NF-κB and its target pro-oncogenes (tumor necrosis factor alpha-induced protein 3 [TNFAIP3]) and genes for growth-related proteins (early growth response protein 1 [EGR1] and growth arrest and DNA-damage-inducible alpha [GADD45a]). The present study provides a new insight into the tumor suppressor roles of CTCF in breast cancer development and suggests that the CTCF/NF-κB pathway is a potential target for breast cancer therapy.CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues. In addition, CTCF expression correlated significantly with cancer stage (P = 0.043) and pathological differentiation (P = 0.029). Furthermore, CTCF overexpression resulted in the inhibition of proliferation, migration, and invasion, while CTCF knockdown induced these processes in breast cancer cells. Transcriptome analysis and further experimental confirmation in MDA-MD-231 cells revealed that forced overexpression of CTCF might attenuate the DNA-binding ability of nuclear factor-kappaB (NF-κB) p65 subunit and inhibit activation of NF-κB and its target pro-oncogenes (tumor necrosis factor alpha-induced protein 3 [TNFAIP3]) and genes for growth-related proteins (early growth response protein 1 [EGR1] and growth arrest and DNA-damage-inducible alpha [GADD45a]). The present study provides a new insight into the tumor suppressor roles of CTCF in breast cancer development and suggests that the CTCF/NF-κB pathway is a potential target for breast cancer therapy.

Establishing age-specific reference intervals for anti-Müllerian hormone in adult Chinese women based on a multicenter population.

AIM OF THIS STUDY Anti-Müllerian hormone (AMH) is useful for the assessment of ovarian reserve and treatment of individualized in vitro fertilization (IVF). The aim of this study is to establish AMH reference interval for adult Chinese women on the Beckman Beckman DxI 800 platform. MATERIAL AND METHODS From May to September 2013, serum from 1169 apparently healthy adult females from five representative cities in China (Beijing, Hangzhou, Guangzhou, Dalian and Urumqi) were collected, and AMH was analyzed on the platform of Beckman DxI 800 automated chemiluminescence immunoassay. Multiple regression analysis was used to investigate the effects of region, sex, age, body mass index (BMI), systolic blood pressure (SBP), exercise on AMH. Age specific reference interval for AMH was established. RESULTS The main factor affecting AMH levels was age (B=-0.756, P<0.001). The AMH reference intervals for adult Chinese women aged 19-24years, 25-29years, 30-34years, 35-39years, 40-44years, 45-49years and ≥50years were 0.74-16.06, 0.67-11.64, 0.50-9.99, 0.09-8.33, 0.04-4.09, 0.01-1.46 and <0.01-0.18ng/ml, respectively. The linear, quadratic and cubic models could either provide good fit regression model to describe the decline of AMH with age (R2=0.40). CONCLUSION This study firstly established age-specific reference intervals for AMH in Chinese women based on multicenter population.