Clinica Chimica Acta

Current research reports and chronological list of recent articles.


The international scientific journal Clinica Chimica Acta publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids, cells or tissues.

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Additional research articles see Current Chemistry Research Articles. Magazines with similar content (clinical chemistry):

 - Clinical Biochemistry.

 - Clinical Chemistry and Laboratory Medicine.

 - Clinical Chemistry Online.

 - Clinical Science.

 - Clinical Toxicology.

 - Journal of Medicinal Chemistry.

 - Journal of Laboratory Medicine.



Clinica Chimica Acta - Abstracts



Comparison of lipoprotein derived indices for evaluating cardio-metabolic risk factors and subclinical organ damage in middle-aged Chinese adults

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Xia Cao, Dongliang Wang, Jiansong Zhou, Zhiheng Chen

Background High-density lipoprotein cholesterol (HDL-C) and related lipoprotein ratios were used to assess lipid atherogenesis or insulin resistance. However, which of these indices is superior remains controversial and could differ across ethnic groups. We evaluated the efficacy of HDL-C, and related lipoprotein ratios in identifying cardio-metabolic risk factors (CMRs) or preclinical organ damage among a health check-ups population in China. Methods We conducted a cross-sectional study of 17,596 Chinese adults aged 40–64years, who participated in annual health checkups in China. Anthropometric, biochemical, liver ultrasound scan, brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT) were analyzed. Partial spearman correlations, receiver operating characteristic (ROC) curves were used for statistical analyses. Results In both gender, the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio consistently had the highest correlation with various CMRs and subclinical organ damage. Overall, the area under the curve (AUC) of TG/HDL-C ratio was significantly greater than that of the rest lipid variables/ratios in the prediction of abdominal obese, high blood pressure, impaired fasting glucose, metabolic syndrome, and preclinical signs of organ damage (all P <0.001). In both gender with a normal TG and HDL-C concentration, those with an increased TG/HDL-C, had higher concentrations of various CMRs and higher presence of subclinical organ damage (despite no significant differences were found between different TG/HDL-C for part of CMRs indicators). Conclusions In this population, TG/HDL-C ratio of ≥1.255 in men and ≥0.865 in women can identify individuals with cardio-metabolic risk, despite TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio seem comparable in their association with CMRs and subclinical signs of organ damage.






Datum: 18.11.2017


Application of digital PCR with chip-in-a-tube format to analyze Adenomatous polyposis coli (APC) somatic mosaicism

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Tomoaki Kahyo, Moriya Iwaizumi, Hidetaka Yamada, Hong Tao, Kiyotaka Kurachi, Haruhiko Sugimura

Background Over the past decade, digital PCR (dPCR) technology has significantly improved, and its application in clinical diagnostics is rapidly advancing. The Clarity™ dPCR platform, which employs the chip-in-a-tube format to broaden its range of applications, has been used to determine gene copy number. However, detection of mutations in human samples, the most demanding task in clinical practice, has not yet been reported using this platform. Methods The Clarity™ dPCR platform was used to detect somatic Adenomatous polyposis coli mosaicism c.834+2T>C, which had been identified using next-generation sequencing (NGS) technology in a patient with sporadic familial adenomatous polyposis. In addition, we were able to determine the size of the dPCR product. Results The mutation rate in the peripheral blood of the patient calculated using the dPCR platform was 13.2%. This was similar to that determined using NGS (12.7%). In contrast, in healthy donors, the mutation rate was <0.1%. Furthermore, it was confirmed that the dPCR product size was consistent with its theoretical value. Conclusion Our results show that the dPCR platform with the chip-in-a-tube format is suitable for the analysis of mosaicism and enables the validation of the dPCR product size.






Datum: 18.11.2017


Critical review of 2016 ACC guidelines on therapies for cholesterol lowering with reference to laboratory testing

Publication date: Available online 2 November 2017
Source:Clinica Chimica Acta

Author(s): Stanley S. Levinson

Introduction This review discusses new guidelines that were released in 2016 and 2017 for assessing risk of coronary disease (ASCVD) and treatments and that appear to have replaced the 2013 guidelines which superseded the National Cholesterol Education Program Adult Treatment Panel Guidelines (ATP). To put the new guidelines in prospective, I briefly review the history of prior guidelines. The newest guidelines seem to support the idea that elevated LDL cholesterol (C) is a cause of ASCVD. The Review also discusses issues related to these guidelines, especially measurement of LDLC, the importance of nonHDLC and puzzling results that do not seem to support the cause and effect idea. Methods Literature review and critical discussion. Conclusions The 2016 guidelines appear to eliminate most of the flaws in the prior 2013 guidelines that replaced the ATP. They do not seem to rely on randomized control studies alone but the totality of all of the evidence. The new guidelines still fail to identify some persons with characteristics of metabolic syndrome that may be of increased risk for ASCVD although they address some of the problems in treating this group. The guidelines identify LDL cholesterol and nonHDL cholesterol target concentrations that are important for laboratory professionals since they should be defined on reports and are important for consultation.






Datum: 18.11.2017


Palestinian Arab ethnicity is associated with an adverse metabolic phenotype

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ram Weiss, Hisham Nassar, Ronit Sinnreich, Wiessam Abu-Ahmad, James Otvos, Jeremy D. Kark

Urban-dwelling Palestinians have been shown to have higher cardiovascular morbidity and mortality and prevalence of diabetes than urban Israelis. Inflammation is implicated in the etiology of these conditions. We hypothesized that increased inflammatory activation, manifested as increased GlycA, a novel biomarker of global inflammation, would be evident in Palestinians. We compared GlycA concentrations between Palestinians and Israelis and assessed the associations of GlycA with anthropometric, health behavioral and clinical variables in a sample of 1674 Palestinians and Israelis aged 25–74, residing in Jerusalem. The main outcome measure was GlycA concentration. GlycA was higher in Palestinians than Israelis (p <0.001). This finding persisted in young Palestinians with normal glucose tolerance. GlycA, total white blood cell count, the triglyceride to HDL-cholesterol ratio and small LDL-cholesterol particles were all significantly higher in Palestinians compared to Israelis across obesity and glucose tolerance categories. Palestinian women had greater GlycA compared to Israeli women and men of both ethnicities. GlycA as well as adverse cardiovascular biomarkers are all higher in Palestinian Arabs than Israeli Jews, even in young healthy adults. This propensity to inflammation may be a driver of the higher risk of cardiovascular disease, insulin resistance and diabetes observed in this population.






Datum: 18.11.2017


Pyroptosis and its relationship to atherosclerosis

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): Yuan-Jun Xu, Lei Zheng, Yan-Wei Hu, Qian Wang

Pyroptosis is a pro-inflammatory form of regulated cell death and is dependent on the enzymatic activity of inflammatory proteases that belong to the family of cysteine-dependent aspartate-specific proteases (caspases). Pyroptosis is morphologically, mechanistically, and pathophysiologically distinct from other forms of cell death, including apoptosis and necrosis. Pyroptosis is characterized by rapid plasma membrane rupture, with the consequent release of intracellular contents and pro-inflammatory mediators, including interleukin (IL)-1β, IL-18, and the alarmin HMGB-1.Recent studies have shown that pyroptosis may be involved in atherosclerosis and play an important role in atherosclerotic lesion instability. Here, we review the progress made in understanding the morphological, molecular, and pathophysiological mechanisms of pyroptosis and its potential role in atherosclerosis.






Datum: 18.11.2017


Urinary metabolic phenotyping of mucopolysaccharidosis type I combining untargeted and targeted strategies with data modeling

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Abdellah Tebani, Isabelle Schmitz-Afonso, Lenaig Abily-Donval, Bénédicte Héron, Monique Piraud, Jérôme Ausseil, Anais Brassier, Pascale De Lonlay, Farid Zerimech, Frédéric M. Vaz, Bruno J. Gonzalez, Stephane Marret, Carlos Afonso, Soumeya Bekri

Background Application of metabolic phenotyping could expand the pathophysiological knowledge of mucopolysaccharidoses (MPS) and may reveal the comprehensive metabolic impairments in MPS. However, few studies applied this approach to MPS. Methods We applied targeted and untargeted metabolic profiling in urine samples obtained from a French cohort comprising 19 MPS I and 15 MPS I treated patients along with 66 controls. For that purpose, we used ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry following a protocol designed for large-scale metabolomics studies regarding robustness and reproducibility. Furthermore, 24 amino acids have been quantified using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Keratan sulfate, Heparan sulfate and Dermatan sulfate concentrations have also been measured using an LC-MS/MS method. Univariate and multivariate data analyses have been used to select discriminant metabolites. The mummichog algorithm has been used for pathway analysis. Results The studied groups yielded distinct biochemical phenotypes using multivariate data analysis. Univariate statistics also revealed metabolites that differentiated the groups. Specifically, metabolites related to the amino acid metabolism. Pathway analysis revealed that several major amino acid pathways were dysregulated in MPS. Comparison of targeted and untargeted metabolomics data with in silico results yielded arginine, proline and glutathione metabolisms being the most affected. Conclusion This study is one of the first metabolic phenotyping studies of MPS I. The findings might help to generate new hypotheses about MPS pathophysiology and to develop further targeted studies of a smaller number of potentially key metabolites.






Datum: 18.11.2017


Diacylglycerols as biomarkers of sustained immune activation in Proteinopathies associated with dementia

Publication date: Available online 13 November 2017
Source:Clinica Chimica Acta

Author(s): Paul L. Wood, John E. Cebak, Randall L. Woltjer

Cognitive decline is a devastating clinical condition, heavily correlated with age progression. In the cases of Alzheimer's disease, Parkinson's disease, and Lewy body disease, the common neuropathologies are proteinopathies and neuroinflammation. Herein, we review current lipidomics findings and conclude that brain and circulating diacylglycerols represent biomarkers of this ongoing sustained immune response, presumably involving microglia. We further hypothesize that a logical next step will be to evaluate biomarkers of immune activation in a cohort of patients with Mild Cognitive Impairment (MCI) and subsequently attempt to provide therapeutic intervention with anti-inflammatory therapy in MCI patients with immune activation. Although this is an urgent and theoretically safe therapeutic trial, it will likely necessitate government support.






Datum: 18.11.2017


NAFL screening score: A basic score identifying ultrasound-diagnosed non-alcoholic fatty liver

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Yu-Jie Zhou, Yi-Fan Zhou, Ji-Na Zheng, Wen-Yue Liu, Sven Van Poucke, Tian-Tian Zou, Dong-Chu Zhang, Shengrong Shen, Ke-Qing Shi, Xiao-Dong Wang, Ming-Hua Zheng

Background Several non-invasive diagnostic scores for non-alcoholic fatty liver (NAFL) have been developed, but the clinical application is limited because of their complexity. Aim To develop and validate an easy-to-calculate scoring system to identify ultrasound-diagnosed NAFL. Methods 48,489 patients from 2 centers were included in this study. Multivariable logistic regression models were employed for model development. Ultrasonography was applied to diagnose NAFL. The selected variables were assigned an integer score proportional to the estimated coefficient from the logistic regression analysis, namely NAFL Screening Score (NSS). The ability of the NSS to identify NAFL was assessed by analyzing the area under the receiver operating characteristic curve (AUROC) and was tested in an independent validation cohort. Additionally, the performance of NSS was compared with existing models. Results NSS was developed as a basic score comprising of age, body mass index (BMI), triglyceride (TG), ALT/AST, fasting plasma glucose (FPG) and uric acid (UA) in both sexes. NSS showed a relatively good discriminative power (AUROC=0.825 for males, 0.861 for females in the validation cohort) in comparison with other models. The optimal cut-off point was 32 for males and 29 for females. Conclusion We developed and validated NSS, an easy-to-use score sheet identify ultrasound-diagnosed NAFL. NSS may be clinically useful for initial diagnosing NAFL.






Datum: 18.11.2017


Serum anti-PLA2R antibody as a diagnostic biomarker of idiopathic membranous nephropathy: The optimal cut-off value for Chinese patients

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): Yipeng Liu, Xuan Li, Chaoqun Ma, Ping Wang, Ju Liu, Hong Su, Hao Zhuo, Xianglei Kong, Dayu Xu, Dongmei Xu

Background The M-type phospholipase A2 receptor (PLA2R) is a specific target autoantigen identified in idiopathic membranous nephropathy (IMN). The autoantibody against PLA2R (anti-PLA2R) may be used to diagnose IMN. However, the appropriate diagnosis cut-off value for Chinese patients with IMN has not been established. Methods In total, 119 patients who underwent renal biopsy (57 patients with IMN and 62 patients with non-IMN glomerulonephritis) and 22 healthy individuals were recruited for our observation study from Qianfoshan Hospital between September 2011 and March 2016. The serum concentration of anti-PLA2R was measured using a quantitative enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and receiver operating characteristic (ROC) curve of anti-PLA2R in diagnosing IMN were analysed based on the ELISA detection. Results The sensitivity, specificity, PPV, and NPV of anti-PLA2R in the diagnosis of IMN in the Chinese patients were 82.5, 75, 69.1, and 86.3% for the 2RU/ml cut-off value; 78.9, 91.7, 86.5, and 86.5% for the 2.6RU/ml cut-off value; 59.6, 95.2, 89.5, and 77.7% for the 14RU/ml cut-off value; 50.9, 96.4, 90.6, and 74.3% for the 20RU/ml cut-off value; and 47.4, 97.6, 93.1, and 73.2% for the 40RU/ml cut-off value, respectively. The area under the ROC curve was 0.879. Conclusions The cut-off value of 2.6RU/ml is recommended for the use of anti-PLA2R for the diagnosis of IMN in Chinese patients based on the ELISA.






Datum: 18.11.2017


Association of serum asymmetric dimethylarginine, homocysteine, and l-arginine concentrations during early pregnancy with hypertensive disorders of pregnancy

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ei Maruta, Jingwen Wang, Tomomi Kotani, Hiroyuki Tsuda, Tomoko Nakano, Kenji Imai, Seiji Sumigama, Yoshimitsu Niwa, Takashi Mitsui, Shigeru Yoshida, Mamoru Yamashita, Akihiro Nawa, Koji Tamakoshi, Hiroaki Kajiyama, Fumitaka Kikkawa

Background Our previous study suggested that a lower l-arginine level (<70μM) at early gestation is associated with pregnancy-induced hypertension. The maternal asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations also have been reported to be increased in hypertensive disorders of pregnancy (HDP). These molecules have a key role in metabolism of nitric oxide. The aim of this study is to determine the most useful predictor of HDP at early gestation. Methods The concentrations of ADMA and Hcy at each of three periods in normal pregnancy were determined, and the values compared between the normal pregnancy and HDP groups. Moreover, the possible risk factors for the development of HDP also were evaluated using a multivariate logistic regression model and propensity score (PS). Results The maternal ADMA concentration was significantly elevated with advance of gestational age, while Hcy concentration was decreased from early to mid-gestation and increased from mid- to late-gestation in normal pregnancy. The maternal Hcy concentration at early gestation was significantly higher in the HDP group compared to that in the normal group. A higher maternal Hcy level (>7.2μM) in early pregnancy was independently associated with the development of HDP (PS-adjusted odds ratio=4.47, 95% confidence interval=1.51–12.82), as well as pre-pregnancy overweight [body mass index (BMI)>25kg/m2], primipara status, and a lower maternal l-arginine level (<70μM). Conclusions The risk factors, such as overweight (BMI>25kg/m2) before pregnancy, primipara status, higher Hcy (>7.2μM), and lower l-arginine (<70μM) concentration in early pregnancy, for development of HDP were detected.






Datum: 18.11.2017


The effect of combined diet and exercise intervention on body weight and the serum GPIHBP1 concentration in overweight/obese middle-aged women

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Masashi Aruga, Yoshiharu Tokita, Katsuyuki Nakajima, Keiko Kamachi, Akira Tanaka

Background The relationship between the effects of diet and exercise intervention and the body weight associated with the serum lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1) concentrations has not been elucidated. Methods Sixty-six overweight/obese middle aged women were assigned to the diet and exercise intervention for 4months. They were divided into 2 groups followed by the body mass index (BMI) decreased >3% (n =41) and <3% (n =25). Serum lipids, lipoproteins and the LPL, HTGL, GPIHBP1 concentrations were determined. Results The cases in which the BMI decreased >3% exhibited significant improvement of diagnostic markers compared with the cases with <3% decrease after the intervention. The LPL concentration did not significantly change, but GPIHBP1 increased significantly after the intervention. The increased GPIHBP1 was significantly associated with decreased body weight. Multiple regression analysis indicated a strong association between GPIHBP1 and percentage of body fat. Conclusions The diet and exercise intervention significantly increased the serum GPIHBP1 concentration in association with a decrease in body weight and percentage of body fat. These results suggest that GPIHBP1 is a better marker for body weight decrease than LPL.






Datum: 18.11.2017


Circulating long non-coding RNA AFAP1-AS1 is a potential diagnostic biomarker for non-small cell lung cancer

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Wei Li, Na Li, Xinmei Kang, Ke Shi

Background Recent studies have indicated that long non-coding RNA actin filament–associated protein 1 antisense RNA 1 (lncRNA AFAP1-AS1) was increased in non–small cell lung cancer and associated with unfavorable patient prognosis. AFAP1-AS1 also participates in promoting invasion and metastasis in non–small cell lung cancer cells. However, the diagnosis value of serum AFAP1-AS1 in non–small cell lung cancer was unclear. In this study, we aimed to explore whether circulating AFAP1-AS1 can be used as a diagnostic biomarker for non–small cell lung cancer. Method The serum AFAP1-AS1 expression level in 126 non–small cell lung cancer patients and 60 healthy controls was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The concentrations of serum cyfra21-1 were detected through chemiluminescence method using the Roche Cobas e601. Receiver operating characteristic curve analysis was applied to assess the diagnostic value of serum AFAP1-AS1 and cyfra21-1 in non–small cell lung cancer. Result The results demonstrated that AFAP1-AS1 expression level was significantly elevated in non–small cell lung cancer patients compared with that in normal controls (p =0.000). Serum AFAP1-AS1 could be used as molecular marker for distinguishing non–small cell lung cancer patients from healthy people with an area under the curve of 0.759 (95% confidence interval=0.692–0.826; p =0.000). The combination of FAP1-AS1 and cyfra21-1 showed that the area under the curve was 0.860 (95% confidence interval=0.808–0.912; p =0.000). Further analysis found that high serum AFAP1-AS1 expression levels correlated with distant metastasis (p =0.03), lymph node metastasis (p =0.017), poor clinical stage (p =0.019), and larger tumor size (p =0.015). Furthermore, AFAP1-AS1 was significantly upregulated in positive distant metastasis group (p =0.003), positive lymph node metastasis (p =0.017), poor clinical stage group (p =0.019), and larger tumor size group (p =0.015). Conclusion Serum AFAP1-AS1 could serve as an ideal combined biomarker for the diagnosis of non–small cell lung cancer.






Datum: 18.11.2017


The Simultaneous measurement of serum testosterone and 5α-dihydrotestosterone by gas chromatography–mass spectrometry (GC–MS)

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): Frank Kannenberg, Manfred Fobker, Erhard Schulte, Grzegorz Pierściński, Reinhard Kelsch, Michael Zitzmann, Jerzy-Roch Nofer, Andreas N. Schüring

Background Simultaneous measurement of testosterone (T) and 5α-dihydrotestosterone (DHT) is important for diagnosing androgen deficiency states and hyperandrogenism in males and females, respectively. However, immunoassays used for T and DHT determination suffer from inadequate specificity and sensitivity, while tandem mass spectrometry is expensive and demanding in use. Methods and results We developed a selective gas chromatography–mass spectrometry (GC–MS) method for parallel T and DHT measurement. The assay showed a linear response up to 46.5nmol/L, intra- and interassay imprecision and inaccuracy <15% and recoveries in spiked samples >90% for both analytes. The limit of quantitation was 0.117nmol/L for T and 0.168nmol/L for DHT. Comparison with immunoassays revealed good agreement for T in males, but a bias in favour of immunoassays at low concentrations for T in females and DHT in both sexes. We established reference ranges for T and DHT and suggest interval partitioning for T according to age in men and menstrual cycle in women. Assay validation in a clinical setting suggests that measuring DHT or T/DHT ratio may help identify patients with polycystic ovary syndrome. Conclusion We developed a selective, simple and inexpensive GC–MS method for parallel measurement of T and DHT with potential use in the clinical laboratory.






Datum: 18.11.2017


An effective algorithm for the serological diagnosis of idiopathic inflammatory myopathies: The key role of anti-Ro52 antibodies

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): M. Infantino, M. Manfredi, V. Grossi, M. Benucci, G. Morozzi, E. Tonutti, M. Tampoia, N. Bizzaro

Background Patients with suspected idiopathic inflammatory myopathies (IIM) are commonly tested for the presence of anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cell substrates. However, ANA-IIF false negative tests may occur in IIM because some antigens, such as Jo1 and Ro52, may be scarcely expressed on HEp-2 cells. In addition, cytoplasmic staining is often not appropriately investigated by a specific antibody assay, leading to decreased clinical sensitivity of the ANA test. We evaluated the diagnostic impact of different strategies using different combination of myositis-related autoantibody tests. Methods Sera from 51 patients with an established diagnosis of IIM were tested for ANA by IIF on HEp-2 cells and for myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) by lineblot methods. Results Forty-four/51 (86.3%) samples tested positive with at least one of the three methods and seven were negative with all methods. Of the 44 positive samples, 9 (20.5%) tested negative for the ANA-IIF test and positive for MAA/MSA. Anti-Ro52 were the most prevalent autoantibodies in IIM patients (21/51; 41%), frequently associated with anti-Jo1 antibodies (13/21; 62%). 13 (16%) anti-Ro52 and anti-Jo1 negative samples were reactive to MSA. Conclusions Our findings suggest that when IIM is clinically suspected, the optimal diagnostic algorithm is to associate the ANA-IIF screening test with a specific test for anti-Ro52 and anti-Jo1 antibodies. Should all these tests be negative, serological tests for MSA are recommended.






Datum: 18.11.2017


Concordance between direct and indirect measurements of free 25-OH vitamin D

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Pilar Peris, Xavier Filella, Ana Monegal, Nuria Guañabens, Laura Foj, María Bonet, Dolors Boquet, Enrique Casado, Dacia Cerdá, Alba Erra, Carmen Gómez-Vaquero, Silvia Martínez, Nuria Montalá, Concepción Pittarch, Eduardo Kanterewicz, Miquel Sala, Xavier Suris, Josep L. Carrasco

At present, data comparing the quantification methods for measurement of free vitamin D (direct assay [direct 25-OHDF] and estimated by calculation [calculated 25-OHDF]), are scarce. The aim of this study was to analyse the concordance between these two methods of 25-OHDF analysis (direct vs. calculated). Methods Serum values of total 25-OHD (25-OHDT), vitamin D binding protein (DBP) (by R&D Systems ELISA), calculated 25-OHDF (by DBP, albumin and 25-OHDT) and direct 25-OHDF (by DIAsource ELISA) were analysed in 173 healthy women (aged 35–45years). Assessment of concordance was evaluated by the Bland-Altman plot and the total deviation index (TDI). Results The mean values of calculated and direct 25-OHDF in these subjects were 5.27±2.5 and 3.83±1.01pg/mL, respectively. We found significantly lower values of 25-OHDF on comparing subjects with and without vitamin D deficiency, independently of the method used. The total deviation index evaluated by the Bland-Altman plot showed low concordance for both measurements. Only low 25-OHDF levels were concordant. Conclusions This study shows that the concordance between these two methods of 25-OHDF analysis is low and has a concentration dependent bias. Further studies are necessary to clarify the reference values and the indications for 25-OHDF measurement.






Datum: 18.11.2017


Bile acid profiles in neonatal intrahepatic cholestasis caused by citrin deficiency

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ching-Hsuan Yang, Chiung-Yu Chen, Yen-Yin Chou, Hung-Chih Chiu, Wei-Lun Tsai, Shu-Chu Shiesh

Background Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by conjugated hyperbilirubinemia and increased plasma bile acid concentrations. However, the underlying mechanisms remain unclear. We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants. Methods We measured 15 bile acids within 15min and found a wide linear range for individual bile acids. Results The within-run and run-to-run CV of all bile acids was 1.2–10.9% and 3.1–10.8%, respectively, with a mean recovery of 90.5–112.6%. Compared to infants with citrullinemia without mutations in SLC25A13 (non-NICCD), NICCD infants showed increased plasma total bile acid concentrations (mean: 201 vs. 42μM, p<0.001), with a distinct bile acid profile characterized by increased conjugated primary bile acid concentrations. The calculated ratios, including primary/secondary bile acid (714 vs. 235, p<0.05) and conjugated/free bile acid (371 vs. 125, p<0.05) ratios, were higher in NICCD infants. The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713–1.0). Conclusions Together, our findings indicated plasma bile acid profile as a potential noninvasive diagnostic biomarker for NICCD.






Datum: 18.11.2017


A monoclonal antibody to the reactive centre loop (RCL) of human corticosteroid-binding globulin (CBG) is a readout for a functional test of pancreatic elastase sufficiency

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): John G. Lewis, Peter A. Elder








Datum: 18.11.2017


Analytical comparison of three different versions of a high-sensitivity cardiac troponin I assay over 10years

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Peter A. Kavsak, Andrew Worster, Stephen A. Hill, Andrew R. MacRae, Allan S. Jaffe

Background Concerns have been raised on the long-term analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays with respect to different reagent formulations, lots and instrumentation. Our goal for the present study was to compare three different versions of an hs-cTnI assay in two different study populations to evaluate if assay re-formulation over 10years has also affected the analytical results. Methods Beckman Coulter's CE marked hs-cTnI assay (Access hsTnI, 2017) was tested in 100 lithium heparin plasma samples first tested in 2007 with their prototype hs-cTnI assay and in 100 serum samples tested with their enhanced hs-cTnI assay in 2011 with comparison performed by Passing-Bablok regression. The Beckman Coulter hs-cTnI results from 2017 and 2011 from the serum samples were also compared to the Abbott ARCHITECT i1000 hs-cTnI results (2013) with 3-fold differences used to identify possible outliers. Freeze/thaw stability testing (−20°C) was also performed on normal cTnI (Beckman=4.0ng/L; Abbott=5.3ng/L) and high cTnI concentration (Beckman=77.6ng/L; Abbott=126.1ng/L) lithium heparin plasma pools for both hs-cTnI assays. Results After 3 freeze-thaws the Beckman hs-cTnI assay yielded minor decreases in concentrations (normal pool −0.7ng/L and high pool −12.6ng/L lower). Regression analyses yielded the following relationship between the Beckman hs-cTnI versions: 2017 hs-cTnI=2.0*(2007 prototype hs-cTnI)-5.1ng/L and 2017 hs-cTnI=1.04(2011 enhanced hs-cTnI)-2.5ng/L. Compared to the Abbott 2013 hs-cTnI results, the 2011 Beckman enhanced version had 8 results 3-fold higher, with the 2017 Beckman version yielding 6 results 3-fold lower. Conclusions: The 2017 Beckman hs-cTnI version (Access hsTnI) is closely aligned with the previous enhanced hs-cTnI assay and appears to have reduced the frequency of aberrantly high results.






Datum: 18.11.2017


Fibroblast growth factor 21 in chronic kidney disease

Publication date: Available online 3 November 2017
Source:Clinica Chimica Acta

Author(s): Sahapab Anuwatmatee, Shudi Tang, Ben J. Wu, Kerry-Anne Rye, Kwok Leung Ong

The association between fibroblast growth factor 21 (FGF21) and kidney function has been extensively studied in recent years in both animal and human studies. However, the exact functional role of FGF21 in the kidney remains unclear. Previous animal studies have shown that administration of FGF21 ameliorates kidney function, morphological glomerular abnormalities, dyslipidemia, hyperglycemia, insulin resistance, oxidative stress and obesity. In human studies, FGF21 levels negatively correlated with estimated glomerular filtration rate. FGF21 levels were elevated in patients with end-stage renal disease. The elevation of FGF21 levels in presence of kidney disease has also raised questions as to whether FGF21 is a potential biomarker for detecting a decline in renal function. In recent clinical trials, an FGF21 analogue reduced insulin levels and body weight, and ameliorated dyslipidemia in patients with type 2 diabetes mellitus and obesity, all of which are well-known risk factors for kidney disease. Thus, FGF21 may be a potential therapeutic target for the treatment of kidney disease, although adverse side effects should also be considered when administering FGF21 since FGF21 may affect bone development and reproduction. This review will assess current knowledge on the relationship between FGF21 and kidney function.






Datum: 18.11.2017


Comparison of plasma copeptin and multiple biomarkers for assessing prognosis of patients with aneurysmal subarachnoid hemorrhage

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Yong-Ke Zheng, Xiao-Qiao Dong, Quan Du, Hao Wang, Ding-Bo Yang, Qiang Zhu, Zhi-Hao Che, Yong-Feng Shen, Li Jiang, Wei Hu, Ke-Yi Wang, Wen-Hua Yu

Background Increased plasma copeptin concentrations are related to poor prognosis after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess prognostic significance of plasma copeptin detection compared with glial fibrillary astrocyte protein, myelin basic protein, S100B, phosphorylated axonal neurofilament subunit H, neuron-specific enolase, tau and ubiquitin carboxyl-terminal hydrolase L1 in aSAH. Methods We detected plasma concentrations of the aforementioned biomarkers in 105 healthy controls using ELISA. Their predictive ability for symptomatic cerebral vasospasm and 6-month poor outcome (Glasgow Outcome Scale score of 1–3) were compared. Results Plasma concentrations of the preceding biomarkers were highly correlated with World Federation of Neurological Surgeons subarachnoid hemorrhage scale (WFNS) scores as well as were significantly higher in patients with symptomatic cerebral vasospasm than in those without symptomatic cerebral vasospasm and in patients with poor outcome than in those with good outcome. In terms of area under receiver operating characteristic curve, their predictive value for symptomatic cerebral vasospasm and 6-month poor outcome was in the range of WFNS scores. Plasma copeptin concentration, but not plasma concentrations of other biomarkers, statistically significantly improved the predictive performance of WFNS scores. Conclusions Copeptin in plasma might have the potential to be a useful prognostic biomarker for aSAH.






Datum: 18.11.2017


An implication of Klotho-related molecules in different smoking-related health outcomes between men and women

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): Kaori Nakanishi, Makoto Nishida, Ryohei Yamamoto, Masahiro Koseki, Toshiki Moriyama, Keiko Yamauchi-Takihara

Background Men and women react differently to some disease states, and women are reported to be more sensitive than men to the toxic effects of smoking. We examined the serum concentration of Klotho-related molecules, α-Klotho (αKl) and fibroblast growth factor (FGF)-21, and the influence of smoking on these molecules in both sexes. Methods Subjects included 90 men and 140 women in good health who underwent a health examination. Results Among male subjects, serum concentrations of FGF-21, soluble sαKl, and inflammation-related cytokine interleukin (IL)-6 were significantly higher in smokers than in never-smokers. In females, serum concentrations of FGF-21 and IL-6 were significantly higher in smokers than in never-smokers; however, sαKl concentrations were slightly lower in smokers than in never-smokers. Serum concentrations of sαKl were correlated with smoking status and IL-6 only in male subjects, suggesting an anti-inflammatory effect of sαKl only in men. Serum concentrations of FGF-21 were correlated with the concentrations of total cholesterol, triglycerides, and HbA1c, which are important factors of metabolic disorders in females, suggesting that metabolic disorders in female smokers may be more serious than that in male smokers. Conclusions Klotho-related molecules showed a differential association and response to smoking between men and women.






Datum: 18.11.2017


First report on an X-linked hypohidrotic ectodermal dysplasia family with X chromosome inversion: Breakpoint mapping reveals the pathogenic mechanism and preimplantation genetics diagnosis achieves an unaffected birth

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Tonghua Wu, Biao Yin, Yuanchang Zhu, Guangui Li, Lijun Ye, Desheng Liang, Yong Zeng

Background To investigate the etiology of X-linked hypohidrotic ectodermal dysplasia (XLHED) in a family with an inversion of the X chromosome [inv(X)(p21q13)] and to achieve a healthy birth following preimplantation genetic diagnosis (PGD). Methods Next generation sequencing (NGS) and Sanger sequencing analysis were carried out to define the inversion breakpoint. Multiple displacement amplification, amplification of breakpoint junction fragments, Sanger sequencing of exon 1 of ED1, haplotyping of informative short tandem repeat markers and gender determination were performed for PGD. Results NGS data of the proband sample revealed that the size of the possible inverted fragment was over 42Mb, spanning from position 26, 814, 206 to position 69, 231, 915 on the X chromosome. The breakpoints were confirmed by Sanger sequencing. A total of 5 blastocyst embryos underwent trophectoderm biopsy. Two embryos were diagnosed as carriers and three were unaffected. Two unaffected blastocysts were transferred and a singleton pregnancy was achieved. Following confirmation by prenatal diagnosis, a healthy baby was delivered. Conclusions This is the first report of an XLHED family with inv(X). ED1 is disrupted by the X chromosome inversion in this XLHED family and embryos with the X chromosomal abnormality can be accurately identified by means of PGD.






Datum: 18.11.2017


The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test

Publication date: January 2018
Source:Clinica Chimica Acta, Volume 476

Author(s): I-Te Lee, Chen-Huan Chen, Jun-Sing Wang, Chia-Po Fu, Wen-Jane Lee, Kae-Woei Liang, Shih-Yi Lin, Wayne Huey-Herng Sheu

Background Arterial stiffening blunts postprandial vasodilatation. We hypothesized that brain-derived neurotrophic factor (BDNF) may modulate postprandial central pulse pressure, a surrogate marker for arterial stiffening. Methods A total of 82 non-diabetic subjects received a 75-g oral glucose tolerance test (OGTT) after overnight fasting. Serum BDNF concentrations were determined at 0, 30, and 120min to calculate the area under the curve (AUC). Brachial and central blood pressures were measured using a noninvasive central blood pressure monitor before blood withdrawals at 0 and 120min. Results With the median AUC of BDNF of 45(ng/ml)h as the cutoff value, the central pulse pressure after glucose intake was significantly higher in the subjects with a low BDNF than in those with a high BDNF (63±16 vs. 53±11mmHg, P =0.003), while the brachial pulse pressure was not significantly different between the 2 groups (P =0.099). In a multivariate linear regression model, a lower AUC of BDNF was an independent predictor of a higher central pulse pressure after oral glucose intake (linear regression coefficient0.202, 95% confidence interval0.340 to −0.065, P =0.004). Conclusion After oral glucose challenge, a lower serum BDNF response is significantly associated with a higher central pulse pressure.






Datum: 18.11.2017


Combined use of serum gamma glutamyl transferase level and ultrasonography improves prediction of perinatal outcomes associated with preeclamptic pregnancy

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Juan Wu, Wei Zhou, Quanhua Li, Rui Yuan, Hezhou Li, Shihong Cui

Introduction Serum gamma glutamyl transferase (GGT), produced and released mostly from the liver and bile duct, is an enzyme involved in response to oxidative stress, and has been used as a maker for prediction of cardiovascular events. Umbilical artery blood flow resistance index, e.g., the systolic/diastolic ratio (S/D ratio) as determined by ultrasound, has been used to assess the fetal intrauterine conditions. While changes of GGT and S/D ratio in preeclampsia are found to be associated with the risk for adverse perinatal outcome, the potential value of combined use of the two measurements for the prediction of adverse perinatal outcome has not been determined. Materials and methods This study included severe preeclampsia patients in late pregnancy and determined their serum GGT levels and ultrasonic flow resistance index of umbilical artery within a week before delivery. Demographic data and perinatal outcomes including perinatal death, five-minute Apgar score, admission to neonatal intensive care unit, respiratory distress syndrome, and intrauterine growth restriction, are documented and analyzed. Results It was found that serum GGT combined with umbilical artery S/D ratio predicted perinatal adverse outcomes in severe preeclampsia patients with a sensitivity of 94.30% and a specificity of 80.00%. Moreover, absent or reversed UA diastolic blood flow was found to be an independent risk factor for intrauterine growth restriction. Conclusion GGT in combination with umbilical artery S/D ratio is a potentially useful marker for the prediction of adverse outcome in severe preeclampsia patients. Future studies in a larger cohort of patients should be performed to verify the efficacy of the strategy. Early and accurate prediction of adverse perinatal events can facilitate the efforts to improve the perinatal outcomes of neonates associated with preeclamptic pregnancies.






Datum: 18.11.2017


Editorial board member, Aims and Scope, Publication Info..

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475










Datum: 18.11.2017


Urinary and circulating levels of the anti-angiogenic isoform of vascular endothelial growth factor-A in patients with chronic kidney disease

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ryosuke Kikuchi, Yoshinari Yasuda, Masahiro Nakatochi, Yohei Shibata, Toshiaki Hara, Atsuo Suzuki, Takahiro Imaizumi, Susumu Suzuki, Hideki Ishii, Kyosuke Takeshita, Tadashi Matsushita, Shoichi Maruyama, Toyoaki Murohara

Introduction The protective effects of vascular endothelial growth factor (VEGF)-A165b on kidney tissue have been suggested in animal studies. However, the relevance of urinary and circulating VEGF-A165b levels in chronic kidney disease patients remains unclear. Therefore, the present study aimed to investigate the urinary and circulating VEGF-A165b levels in patients with chronic kidney disease. Methods This observational study enrolled a total of 92 Japanese patients with chronic kidney disease, who had undergone inulin renal clearance measurements for the accurate assessment of measured GFR. Urinary or circulating total VEGF-A and VEGF-A165b levels were measured using enzyme-linked immunosorbent assay. Results Urinary VEGF-A165b levels were significantly lower in G3a, G3b, and G4+G5 category patients than in G1+G2 category patients. Correlation analysis found that serum creatinine levels, serum cystatin C levels, eGFRcre, eGFRcys, and mGFR were weakly but significantly correlated with urinary VEGF-A165b levels. Additionally, circulating VEGF-A165b levels were significantly higher in G4+G5 category patients than in G1+G2 category patients. Conclusion A low urinary VEGF-A165b level reflects renal dysfunction in the chronic kidney disease stage, while a high circulating VEGF-A165b level cannot be attributed to decreased renal clearance.






Datum: 18.11.2017


Transplantation routes affect the efficacy of human umbilical cord mesenchymal stem cells in a rat GDM model

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Dan Wu, Shan Zou, Haibin Chen, Xiaoyan Li, Yetao Xu, Qing Zuo, Yi Pan, Shi-Wen Jiang, Huan Huang, Lizhou Sun

Gestational diabetes mellitus (GDM) is harmful to both the mother and fetus. Although transplantation of human umbilical cord mesenchymal stem cells (HUMSCs) could be a useful therapy for GDM, the influences of different transplantation routes on the therapeutic effects remain unclear. In this study, we isolated and cultured the HUMSCs for transplantation, and the biological activity of HUMSCs was verified by flow cytometric analysis (the positive markers, CD44, CD73, CD105 and CD90, the negative markers, CD45, CD34, CD19, HLA-DR, and CD11b) and potency of osteogenic, adipogenic and chondrogenic differentiation. Streptozotocin (STZ)-induced diabetes mellitus (DM)/GDM rats were transplanted with HUMSCs by different routes: single or multiple tail vein injection, liver parenchyma, and renal capsule transplantation. These were compared to positive controls (STZ-induced, untreated) and negative controls (non-induced, untreated) to determine the effect of the transplant on the control of DM/GDM. The blood glucose level and body weight of rats in each group were determined and showed different effects. Transplantation of HUMSCs to GDM rats can increase the number of offspring in comparison to the negative controls. The weight of the offspring in the transplantation groups also increased due to the therapeutic effect of HUMSCs. Based on results, we concluded that transplanting HUMSCs could effectively alleviate the symptoms of elevated blood glucose and weight loss and improve the body weight and survival rate of offspring. Injections of HUMSCs were required to persistently decrease the blood glucose of DM and GDM rats. Transplanting HUMSCs into the liver or renal capsule of GDM rats led to a similar efficiency of controlling blood glucose and compensation for body weight. HUMSCs therapy increased the number and body weight of offspring and improved their activity. In summary, this study has enabled progress toward determining the optimal route for GDM therapy.






Datum: 18.11.2017


A new plasma biomarker enhance the clinical prediction of postoperative acute kidney injury in patients with hepatocellular carcinoma

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Xing Zhou, Liyu Wang, Guoliang Wang, Xiang Cheng, Shaobo Hu, Wenbo Ke, Min Li, Yong Zhang, Zifang Song, Qichang Zheng

Background The ratio of serum γ-glutamyl transferase (GGT) to alanine aminotransferase (ALT) (GGT/ALT) is a marker for evaluating effects to antivirotic treatment and a helpful predictive factor for the prognosis of Child-Pugh A hepatocellular carcinoma (HCC) patients after surgery. The relationship between the incidence of postoperative acute kidney injury (AKI) and preoperative GGT/ALT is studied in hepatectomized hepatitis B- or C– associated HCC patients. Methods A total of 253 hepatitis B or C virus-related HCC patients undergoing hepatectomy between September 2012 and August 2016 at our hospital were included in the retrospective study. Serum ALT and GGT value were recorded, and the GGT/ALT was computed. AKI was defined that based on the “Kidney Disease Improving Global Outcomes (KDIGO) criteria”. Results AKI was observed in 22 (8.7%) patients. Mean GGT/ALT of patients with AKI was significantly higher than in those without it (6.0 vs 2.1, P <0.001). Multivariate analysis revealed an increase in GGT/ALT as an independent risk factor for AKI in hepatitis B- or C- associated HCC patients, particularly in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A staged HCC (odds ratio (OR) 1.400, P <0.001). Multivariate analysis showed that ALT (OR 0.966, P =0.044) was somewhat inversely associated with the incidence of AKI in hepatitis B- or C- associated HCC patients. The best cutoff point of GGT/ALT was 2.92. Multivariate analysis showed that preoperative GGT/ALT ≥2.92 predicted poor prognosis of postoperative AKI in patients with HCC after hepatectomy (odds ratio 17.697, P <0.001). After propensity score matching, preoperative GGT/ALT ≥2.92 remained an independent risk factor for AKI in HCC patients (OR 13.947, P =0.003). Conclusions The GGT/ALT of patients with AKI was significantly higher than those without it. Evaluation of GGT/ALT before surgery can be a helpful predictive tool for postoperative AKI in hepatitis B- or C– associated HCC patients undergoing hepatectomy, particularly in patients with BCLC stage 0 or A staged HCC. Hepatitis B- or C- associated HCC patients with low ALT especially within the normal range may have a high risk of AKI. However, the reason remains to be elucidated.






Datum: 18.11.2017


Copeptin in heart failure: Review and meta-analysis

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Yao Zhong, Rui Wang, Lulu Yan, Man Lin, Xingling Liu, Tianhui You

Background The aim of this study was to explore the prognostic value of copeptin for predicting all-cause mortality in heart failure (HF). Methods PubMed, Embase and Cochrane databases were systematically searched to identify if a 2×2 contingency table could be constructed based on both the copeptin level and the all-cause mortality in patients diagnosed with HF. The characteristics of test performance were summarized using forest plots and summary receiver operating characteristic curves (SROC). Q-test and I2 index were used to evaluate heterogeneity. Results Ten prospective cohort studies comprising 4473 patients were eligible in this meta-analysis. An elevated copeptin level was associated with an increased risk of all-cause mortality in HF patients (Relative risk (RR) was 2.64 (95% CI, 2.09–3.32)). The pooled sensitivity (SEN) and specificity (SPE) of copeptin were 0.57 (95% CI, 0.50–0.63) and 0.74 (95% CI, 0.69–0.79), respectively. The positive likelihood ratio was 2.2 (95% CI, 1.90–2.60) and the negative likelihood ratio was 0.58 (95% CI, 0.52–0.66). Furthermore, the summary Diagnostic Odds Ratio (DOR) was 4.00 (95% CI, 3.00–5.00) and the AUC was 0.70 (95% CI, 0.66–0.74) similar to the AUC of NT-proBNP 0.71 (95% CI, 0.67–0.75). Conclusions Elevated levels of copeptin are associated with all-cause mortality in HF patients. The predictive value of copeptin is comparable with NT-proBNP for all-cause mortality in HF patients. Further studies are warranted to explore the prognostic value of copeptin in conjunction with other biomarkers and to determine an optimal cut-off level.






Datum: 18.11.2017


Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patients and the association with poor treatment outcome at 2months

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Kai Zhao, Xiaoqian Luan, Yuntao Liu, Xinjie Tu, Huijun Chen, Huiping Shen, Huihua Qiu, Zhuoying Zhu, Jincai He

Background The association between low 25-hydroxyvitamin D [25(OH)D] and sleep disorder has been reported. We investigated whether serum concentrations of 25(OH)D are altered in chronic insomnia patients. The relationship between serum concentrations of 25(OH)D and the treatment outcome in patients at 2months was also investigated. Methods In total, 181 chronic insomnia patients were consecutively recruited. All patients received pharmacotherapy for the treatment of chronic insomnia. Serum 25(OH)D concentrations were quantified by a competitive electrochemiluminescence protein binding assay. Treatment outcomes were defined as “response” versus “non-response”, according to the change of the Pittsburgh Sleep Quality Index (PSQI). We also recruited 100 healthy subjects as a control group. Results Fifty-four out of 181 (29.8%) patients met the criteria for non-response. Chronic insomnia patients had significantly lower 25(OH)D concentrations compared with healthy controls (23.01±9.18 vs 27.17±6.41ng/ml, P <0.001). Non-response patients also had significantly lower 25(OH)D concentrations than those with response. Vitamin D deficiency(25(OH)D concentrations<20ng/ml) was independently associated with a higher probability of treatment non-response at 2months (odds ratio 11.636, 95% confidence interval 3.966–34.142, P <0.001). Conclusions Measurement of serum 25(OH)D concentrations are probably useful for judging treatment outcomes of pharmacotherapy in chronic insomnia patients.






Datum: 18.11.2017


C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Zhun Wang, Shuanghe Peng, Aixiang Wang, Hui Xie, Linpei Guo, Ning Jiang, Yuanjie Niu

Background The prognostic value of C-reactive protein (CRP) in metastatic renal cell carcinoma (RCC) patients receiving tyrosine kinase inhibitors (TKIs) has been investigated in previous studies; however, the results remain inconclusive. This study investigated the prognostic value of pretreatment CRP in patients with metastatic RCC treated with TKIs. Methods PubMed, Embase, Web of Science, and Cochrane databases were searched for studies investigating the relationships between pretreatment CRP and prognosis in patients with metastatic RCC. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. Results A total of 1199 patients from nine studies were included in the analysis. The results showed that an elevated CRP level was an effective prognostic marker of both OS (pooled HR=2.87, 95% confidence interval [CI]: 2.34–3.54, p <0.001) and PFS (pooled HR=2.39, 95% CI: 1.75–3.26, p <0.001). Subgroup analysis revealed that an elevated CRP level significantly predicted poor OS and PFS in studies conducted in Japan (OS, pooled HR=3.03, 95% CI: 2.29–4.01, p <0.001; PFS, pooled HR=3.6, 95% CI: 1.62–8.0, p =0.002), and in cut-off value of CRP <0.8 (OS, pooled HR=2.93, 95% CI: 2.21–3.88, p <0.001; PFS, pooled HR=2.57, 95% CI: 1.82–3.65, p <0.001). Conclusions This study suggests that an elevated CRP level is correlated with poor prognosis in patients with metastatic RCC receiving TKIs treatment.






Datum: 18.11.2017


Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of colorectal cancer

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Chung-Wei Fan, Yung-Bin Kuo, Geng-Pin Lin, Si-Min Chen, Shih-Hsien Chang, Bo-An Li, Err-Cheng Chan

Background Colorectal cancer (CRC) is one of the most common malignancies worldwide, and early diagnosis is vital to improving prognoses. We explored the diagnostic potential of a multiplex autoantibody panel as a biomarker for the detection of CRC by ELISA. Methods In total, 192 serum samples (92 CRC and 100 matched controls) were tested against a panel of 12 tumor-associated antigens (TAAs): RPH3AL, RPL36, SLP2, p53, survivin, ANAXA4, SEC61B, CCCAP, NYCO16, NMDAR, PLSCR1, and HDAC5. Individual and combined autoantibody signatures were examined. Results Compared to individual autoantibody markers, the combinations of TAAs provided better discrimination between tumorous and normal sera. The overall sensitivity of a selected panel of four antibodies (anti-SLP2, -p53, -SEC61B, and -PLSCR1) was 64.1%, with a specificity of 80% that increased to 83.7% when carcinoembryonic antigen (CEA) measurement was added. Furthermore, the sensitivity of the panel of four antibodies for early and advanced stages of CRC was 66.7% and 62%, increasing to 88.3% and 84%, respectively, when CEA was added. Conclusions We identified a panel of four antibodies as a promising diagnostic biomarker for the detection of CRC.






Datum: 18.11.2017


Homocysteine in non-valvular atrial fibrillation: Role and clinical implications

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Yan Yao, Mei-sheng Shang, Jian-zeng Dong, Chang-sheng Ma

Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with a series of adverse complications that cause so-called AF socioeconomic burden. Apart from the classical risk factors, it seems to be novel factors that increase the risk of AF and AF-related stroke. Recently, more and more evidence has well documented the close relationships between homocysteine (Hcy) and AF. As a well-known marker for pro-oxidation and pro-inflammation, Hcy plays an important role in a number of vascular diseases having strong association with AF. This review will discuss the expression of Hcy and its association with ischemic stroke in AF patients especially for elderly patients, and the role and clinical implications of Hcy in the thromboembolic events and rhythm outcome in AF patients. The possible mechanisms linking elevated Hcy and cardiovascular events in AF patients will also be addressed, including oxidative stress, inflammatory response, atrial remodeling, etc.






Datum: 18.11.2017


An additional measurement of glycated albumin can help prevent missed diagnosis of diabetes in Chinese population

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Xingxing He, Lingwen Ying, Xiaojing Ma, Yun Shen, Hang Su, Jiahui Peng, Yufei Wang, Yuqian Bao, Jian Zhou, Weiping Jia

Background In subjects who present a first fasting plasma glucose (FPG1) ≥7.0mmol/l without classic symptoms of diabetes, diagnosis of diabetes will likely be missed without an additional oral glucose tolerance test (OGTT) in the Chinese population. Recent studies have shown that glycated albumin (GA) has advantages in reflecting postprandial hyperglycemia. Therefore, the present study evaluated whether additional measurement of GA could reduce the rate of missed diagnosis of diabetes. Methods A total of 1287 participants (711 men, 576 women) with a FPG1 7.0mmol/l without classic symptoms of diabetes were enrolled and underwent a 75-g OGTT. Serum GA was measured by a liquid enzyme method. Diabetes was diagnosed based on the 2010 American Diabetes Association (ADA) criteria. Results A total of 992 (77.08%) participants were diagnosed diabetes by OGTT and glycated hemoglobin A1c (HbA1c). The diagnostic validity of 2-h postload plasma glucose (2hPG) was superior to other glycemic index (the diagnostic sensitivity of 2hPG, HbA1c, the second FPG (FPG2) was 87.50%, 73.99%, 63.21%, respectively). Without 2hPG after OGTT, repeat testing of FPG2 alone would result in missed diagnosis of 36.79% of diabetic participants, whereas testing FPG2 with HbA1c was associated with a missed diagnosis rate of 14.31%. While using the combined criteria of FPG2 7.0mmol/l and/or HbA1c 6.5% and/or GA17.1%, the rate of missed diagnosis was merely 9.48%. That is, the rate of missed diagnosis was reduced by 33.75% with the addition of GA measurement. The k value reflecting the consistency of diagnosis between the FPG2 and/or HbA1c and/or GA criteria and the 2010 ADA criteria was 0.788. Conclusions For subjects with FPG17.0mmol/l without classic symptoms of diabetes, additional measurement of GA can help prevent missed diagnosis of diabetes in Chinese population.






Datum: 18.11.2017


Recognition of rare hemoglobin variants by hemoglobin A1c measurement procedures

Publication date: Available online 14 November 2017
Source:Clinica Chimica Acta

Author(s): Sydney W. Strickland, Sean T. Campbell, Randie R. Little, David E. Bruns, Lindsay A.L. Bazydlo

Background Unrecognized hemoglobinopathies can lead to measured hemoglobin A1c (Hb A1c) concentrations that are erroneous or misleading. We determined the effects of rare hemoglobin variants on capillary electrophoresis (CE) and HPLC methods for measurement of Hb A1c. Methods We prospectively investigated samples in which Hb A1c was measured by CE during a 14-month period. For samples in which the electropherograms suggested the presence of rare hemoglobinopathies, hemoglobin variants were identified by molecular analysis or by comparison with electropherograms of known variants. When sample volume permitted, Hb A1c was measured by 2 HPLC measurement procedures and by boronate affinity HPLC. Results Hb A1c was measured by CE in 33,859 samples from 26,850 patients. 15 patients (0.06%) were identified as having rare hemoglobinopathies: Hbs A2 prime, Agenogi, Fannin-Lubbock I, G Philadelphia, G San Jose, J Baltimore, La Desirade, N Baltimore, Nouakchott, and Roanne. Among 6 of these samples tested by 2 ion-exchange HPLC methods, the rare Hb was detected by both HPLC methods in only one sample, and none were detected by boronate affinity HPLC. The mean of the Hb A1c results of 2 HPLC methods differed from the result of the CE method by 0.7–2.2% Hb A1c in samples with variant hemoglobins versus <0.2% Hb A1c in samples without variants. Conclusion Measurement procedures differ in the ability to detect the presence of rare Hb variants and to quantify Hb A1c in patients who harbor such variants.






Datum: 18.11.2017


External quality assessment program on urinary dysmorphic erythrocytes

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): José Antonio Tesser Poloni, Fernanda Pereira da Silva Carpeggiani, Isabel Antas Tavares da Silva, Janaína A. de Oliveira, Juliana Barroso Tobler, Edmo M. Saldanha, Liane N. Rotta








Datum: 18.11.2017


Metabolomics in gestational diabetes

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Xun Mao, Xuyang Chen, Chang Chen, Hua Zhang, Kai P. Law

Gestational diabetes mellitus (GDM) is a form of diabetes that is first diagnosed during pregnancy in the absence of existing type 1 or type 2 diabetes. Early screening tools for GDM are currently unavailable, but metabolomics is a promising approach for detecting biomarkers of GDM. This review evaluates recent GDM studies employing metabolomic techniques, highlighting the challenges in those studies and envisions the future directions for metabolomic study of GDM. A diverse range of predictive markers and dysregulated metabolic pathways have been associated with the pathogenesis of GDM, but these findings have lacked reproducibility among studies. The case-control study design has been most frequently employed in the studies of GDM, and most of them used specimens acquired in mid-pregnancy. However, this approach might not be adequate to recognise the complexity of the condition. The sample size in some of the studies is limited, and this may result in findings from a participant set that is not representative of the general population. Therefore, we propose that future metabolomic studies pertaining to GDM use a cross-platform approach employing unified diagnostic criteria, a longitudinal cohort, and innovative data processing methods to allow for full-scale identification and comprehensive coverage of the metabolome. In addition, the relationship between the exposure to environmental chemicals such as endocrine disruptors and the development of GDM should be further investigated in future studies.






Datum: 18.11.2017


A review of S100 protein family in lung cancer

Publication date: Available online 13 November 2017
Source:Clinica Chimica Acta

Author(s): Ting Wang, Xiaoying Huo, Zhaoyang Chong, Hamadhaider Khan, Rui Liu, Ting Wang

S100 protein family, representing 25 relatively small calcium binding proteins, has been reported to be involved in multiple stages of tumorigenesis and progression. These proteins are considered having potential value to be adopted as novel biomarkers in the detection and accurate prediction of many kinds of tumors, including lung cancer. As the one having the highest morbidity and mortality among all cancers, lung carcinoma is still occult for detection, especially at early stage. S100 proteins take participation in the lung neoplasia through playing intracellular and/or extracellular functions, therefore getting involved in a variety of biological processes such as differentiation, proliferation, and migration. A few members have also been testified to modulate TGF-β/Smad-3 mediated transcriptional activity of target genes involved in tumor promotion. In addition to that, a number of proteins in this family have already been reported to experience an abnormal trend in lung cancer at cell, serum and tissue levels. Thus, S100 proteins may serve as effective biomarkers for suspected or already diagnosed lung cancer patients. In future, S100 protein family might be applied as therapeutic targets in clinical treatment of lung cancer. In this review, we firstly summed up the biological and clinical evidence connecting S100 proteins and lung cancer, which has not been summarized before.






Datum: 18.11.2017


Elevated serum levels of endothelin-1 in patients with chronic inflammatory demyelinating polyneuropathy

Publication date: Available online 11 November 2017
Source:Clinica Chimica Acta

Author(s): Chun-Wei Chang, Hsiu-Chuan Wu, Rong-Kuo Lyu, Yen-Shi Lo, Chiung-Mei Chen, Long-Sun Ro, Hong-Shiu Chang, Ching-Chang Huang, Ming-Feng Liao, Yih-Ru Wu, Hong-Chou Kuo, Chun-Che Chu, Yi-Ching Weng, Pei-Tsi Wei, Ai-Lun Lo, Kuo-Hsuan Chang

Introduction A Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, or non-hereditary, chronic demyelinating neuropathy. Currently, there is no reliable molecular biomarker that can identify CIDP patients as well as monitor disease severity. Material and methods We measured serum levels of endothelin-1 (ET-1), a factors involved in vasoconstrictive, inflammatory and nerve regenerative processes, in the serum of 20 CIDP, 21 acute inflammatory demyelinating polyneuropathy (AIDP), 37 multiple sclerosis (MS), and 10 Alzheimer's disease (AD) patients, as well as 26 healthy control (HC) subjects. Results Patients with CIDP demonstrated higher serum levels of ET-1 (2.07±1.07pg/mL) than those with those with AIDP (0.75±0.62ng/mL, P <0.001), AD (0.78±0.49pg/mL, P <0.001), as well as HCs (1.16±0.63pg/mL, P =0.002), while levels of ET-1 in patients with MS (2.10±0.81pg/mL) and CIDP were similar. Furthermore, the serum ET-1 levels significantly correlated with Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale in CIDP patients. Receiver operating characteristic (ROC) curve showed good discrimination ability for ET-1 to distinguish CIDP patients from AIDP (AUC=0.883) or HCs (AUC=0.763). Conclusion This study discloses the potential of serum ET-1 as a biomarker for CIDP.






Datum: 18.11.2017


Mutation screening of the GLIS3 gene in a cohort of 592 Chinese patients with congenital hypothyroidism

Publication date: Available online 13 November 2017
Source:Clinica Chimica Acta

Author(s): Chunyun Fu, Shiyu Luo, Xigui Long, Yingfeng Li, Shangyang She, Xuehua Hu, Meizhen Mo, Zhanghong Wang, Yuhua Chen, Chun He, Jiasun Su, Yue Zhang, Fei Lin, Bobo Xie, Qifei Li, Shaoke Chen

Objectives Defects in the human GLI-similar 3 (GLIS3) gene are reported to be a rare cause of congenital hypothyroidism (CH) and neonatal diabetes. The aim of this study was to examine the prevalence of GLIS3 mutation among CH patients in the Guangxi Zhuang Autonomous Region of China and to define the relationships between GLIS3 genotypes and clinical phenotypes. Methods Blood samples were collected from 592 patients with CH in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the GLIS3 gene with their exon-intron boundaries were screened by next-generation sequencing (NGS) and CNVplex®. Chromosomal microarray analysis (CMA) was performed to detect the existence of the adjacent gene deletion. Results NGS and CNVplex® analysis of GLIS3 in 592 CH patients revealed two different variations in two individuals (2/592, 0.3%). Patient 1 was the paternal allele of 9p24.3p23 heterozygous deletion including the whole GLIS3 gene, and patient 2 was heterozygous for c.2159G>A (p.R720Q) GLIS3 variant combined with compound heterozygous DUOX2 mutations (p.R683L/p.L1343F). Conclusions Our study indicated that the prevalence of GLIS3 variations was 0.3% among studied Chinese CH patients. Multiple variations in one or more CH associated genes can be found in one patient. We found a novel GLIS3 variation c.2159G>A (p.R720Q), thereby expanding the variation spectrum of the gene.






Datum: 18.11.2017


Biomarkers of cerebral microembolic signals

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ruihua Yin, Aijun Ma, Xudong Pan, Shaonan Yang

Stroke is a major cause of mortality and morbidity around the world. Microembolic signals (MES), as the markers of unstable atherosclerotic plaque, can predict the occurrence and prognosis of ischemic stroke (IS). MES can also assess the efficacy of antithrombotic agents and predict the recurrence probability of IS. Unstable plaques are the main source of MES; thus, numerous biomarkers of atherosclerotic plaque instability are highly likely to predict the presence of MES. This study aims to review recent biomarker candidates for MES or microembolism. Current research indicates that the following are independent markers for positive MES: high level of serum soluble P-selectin, chemokine (C-X-C motif) ligand 16 (CXCL16) and fibrinogen, high neutrophil count, reduced ratio of CD4+CD25high regulatory T cells (Tregs) and the C allele of tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) rs3102735. However, a more integrated profile of biomarkers for MES is needed to improve the stratification of patients with carotid stenosis and enhance the effectiveness of therapeutic interventions and prevention for IS.






Datum: 18.11.2017


Plasma cell-free DNA level and its integrity as biomarkers to distinguish non-small cell lung cancer from tuberculosis

Publication date: Available online 4 November 2017
Source:Clinica Chimica Acta

Author(s): Shaoyi Leng, Jianjun Zheng, Yinhua Jin, Hongbin Zhang, Ya Zhu, Jing Wu, Yan Xu, Puhong Zhang








Datum: 18.11.2017


Extremely low level of serum pigment epithelium-derived factor is a special biomarker of Chinese osteogenesis imperfecta patients with SERPINF1 mutations

Publication date: Available online 2 November 2017
Source:Clinica Chimica Acta

Author(s): Jian-yi Wang, Lu-jiao Li, Qian Zhang, Yi Liu, Fang Lv, Xiao-jie Xu, Yu-wen Song, Ou Wang, Yan Jiang, Wei-bo Xia, Xiao-ping Xing, Mei Li

Backgrounds SERPINF1 mutations caused deficiency of pigment epithelium-derived factor (PEDF) and would lead to osteogenesis imperfecta (OI) type VI. However, serum PEDF levels were unclear in Chinese OI patients who had clear molecular diagnosis. Objective To assess PEDF levels in different genotypes of OI, to evaluate the influencing factors of PEDF in Chinese OI patients with clear molecular diagnosis. Methods Known candidate genes of OI were examined by a targeted next generation sequence. Serum PEDF levels were measured by ELISA in 6 OI patients with SERPINF1 mutations, 6 carriers of one copy of the SERPINF1 mutation, 88 OI patients with COL1A1, CLO1A2, IFITM5 and other pathogenic mutations of OI and 24 healthy controls. We compared the differences in serum PEDF levels among different OI patients and normal controls. Results Serum PEDF levels were extremely low in OI patients with SERPINF1 mutations (0.66±1.60μg/ml) than in OI patients with other pathogenic mutations (4.88±1.43–7.07±2.43μg/ml), carriers of one copy of SERPINF1 mutation (4.94±2.35μg/ml), and normal controls (7.29±2.31μg/m) (P <0.001). No significant differences in serum PEDF concentrations were found among patients with OI type I, III or IV, and between patients with or without bisphosphonate treatment. Serum PEDF level was positively correlated with Z-score of weight (r=0.310, P =0.004), BMI (r=0.253, P =0.020) and alanine aminotransferase (r=0.291, P =0.007). Conclusions Extremely low level of PEDF was demonstrated as a specific, convenient, and inexpensive diagnostic biomarker for OI patients with SERPINF1 mutations, but it could not provide information regarding the clinical severity of OI and the efficacy of bisphosphonates treatment.






Datum: 18.11.2017


Increased levels of interleukin-22 in thoracic aorta and plasma from patients with acute thoracic aortic dissection

Publication date: Available online 2 November 2017
Source:Clinica Chimica Acta

Author(s): Jing Ye, Menglong Wang, Huimin Jiang, Qingwei Ji, Ying Huang, Jianfang Liu, Tao Zeng, Yao Xu, Zhen Wang, Yingzhong Lin, Jun Wan

Background Interleukin (IL)-22 plays important roles in the development of arterial disease, including atherosclerosis and hypertension. However, the relationship between IL-22 and acute thoracic aortic dissection (TAD) remains unknown. Methods Blood samples were collected from patients with chest pain who underwent computed tomography angiography of the thoracic aorta but had no known preoperative diagnosis of coronary artery disease, peripheral artery disease, arthritis, and/or membranous nephropathy. Patients were divided into non-AD (NAD) and TAD groups, and the plasma concentrations of IL-22, IL-6 and tumor necrosis factor (TNF)-α were measured. In addition, aortic tissue samples from acute TAD patients and normal donors were collected, and the expression levels of IL-22 and IL-22 receptor 1 (IL-22R1) were measured. Results IL-22, IL-6 and TNF-α levels were significantly higher in acute TAD patients than in NAD patients (IL-22, NAD group: 27.0 (19.1, 38.6) pg/ml vs. TAD group: 32.9 (20.6, 58.3) pg/ml, p<0.0001). The correlation analysis showed that IL-22 levels were positively correlated with levels of IL-6, TNF-α, fasting glucose, blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that IL-22 was independently associated with the presence of acute TAD (OR 1.169, 95% CI 1.069 to 1.277; p=0.001). In addition, compared with aortic tissue of normal controls, TAD aortas showed increased expression of IL-22 and IL-22R1, especially in the torn section (IL-22, non-torn section: 2.8±0.5/HPF vs. torn section 2.8±0.5/HPF, p<0.001). Additionally, macrophage but not T lymphocyte infiltration was significantly increased in the torn section (Macrophage, non-torn section: 2.2±0.6/HPF vs. torn section 5.7±1.2/HPF, p<0.001; T lymphocyte, non-torn section: 2.7±0.9/HPF vs. torn section 2.4±0.5/HPF, p=0.28), as evidenced by increased positive staining for the macrophage marker CD68, as opposed to the T cell marker CD3. Conclusion IL-22 levels may correlate with the presence of acute TAD.






Datum: 18.11.2017


LncRNA PANDAR as a prognostic marker in Chinese cancer

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Peng-ju Ma, Qing-kai Guan, Da-wei Xu, Jia Zhao, Nan Qin, Bao-zhe Jin

Background LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors. Methods The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters. Results Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR=1.60, 95% CI: 1.09–2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09–5.09), advanced tumor stage (OR=3.60, 95% CI: 2.39–5.44) and histological grade (OR=2.75, 95% CI: 1.73–4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis. Conclusions Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients.






Datum: 18.11.2017


Circulating asprosin concentrations are increased in type 2 diabetes mellitus and independently associated with fasting glucose and triglyceride

Publication date: Available online 2 November 2017
Source:Clinica Chimica Acta

Author(s): Lei Zhang, Chao Chen, Nan Zhou, Yuming Fu, Xingbo Cheng

Background Asprosin has been identified as a novel hormone enriched in white adipose tissue and is pathologically increased in insulin-resistant mice and humans. However, information regarding the role of asprosin in type 2 diabetes mellitus (T2DM) remains unavailable. Via conducting a hospital-based study, we purposed to ascertain the potential relationship between circulating asprosin concentrations and T2DM. Methods The study recruited 84 adults with T2DM and 86 controls with normal glucose tolerance. They matched in age, body mass index (BMI), and sex. Serum asprosin concentrations were measured via ELISA method. Results Compared to the controls, serum asprosin concentrations were significantly increased in the T2DM adults (P <0.001). As asprosin concentrations increased across its tertiles, the percentage of T2DM increased (39.28, 37.50, and 70.68%; P value for trend <0.001). Multivariate logistic regression models demonstrated that compared with the 1st tertile of asprosin, the odds ratio of T2DM was 3.278(95% CI 1.053–10.200, P =0.040) for the 3rd tertile after adjustment for potential confounders. Area under ROC curve of asprosin (sex and age adjusted) for predicting the presence of T2DM was 0.707[95% CI 0.628–0.786]. Finally, multiple stepwise regression analysis indicated that fasting glucose and triglyceride were independently associated with serum asprosin in T2DM. Conclusions Asprosin concentrations are increased in adults with T2DM. The results suggest that asprosin might serve as a risk factor associated with the pathogenesis of T2DM, but not an ideal biomarker for predicting T2DM.






Datum: 18.11.2017


lncRNA PVT1 in cancer: A review and meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Dapeng Lu, Peng Luo, Qi Wang, Yuanyuan Ye, Baolong Wang

Objectives Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA that functions as an oncogenic molecule in different cancers. We conducted a systematic review and meta-analysis to determine its prognostic potential for malignant tumors. Materials and methods A literature survey was conducted by searching the PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wanfang electronic databases for articles published as of June 1, 2017. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to demonstrate the relationship between PVT1 expression and overall survival (OS) and disease-free survival (DFS) using RevMan 5.2 and Stata 12.0 software. A quality assessment of the included studies was performed according to the Newcastle–Ottawa scale. Results A total of 1443 patients from 15 studies were included in this meta-analysis. Elevated PVT1 expression was significantly correlated with poor overall survival (HR=2.03, 95% CI: 1.69–2.43) and disease-free survival (HR=1.55, 95% CI: 1.29–1.87). Statistical significance was also observed in a subgroup meta-analysis that was stratified by variance analysis, cancer type, sample size and PVT1 cut-off value. Additionally, increased PVT1 expression was significantly associated with positive lymph node metastasis (odds ratio (OR)=1.94, 95% CI: 1.03–3.68), positive distant metastasis (OR=3.85, 95% CI: 2.14–6.93), advanced tumor-node-metastasis stage (OR=3.19, 95% CI: 2.45–4.15) and poor differentiation grade (OR=1.57, 95% CI: 1.15–2.16), but not tumor size (P >0.05). Conclusion Elevated PVT1 expression was related to poor prognosis and might be a potential biomarkerof clinicopathological characteristics in different cancer types. More studies need to be conducted to verify the clinical value of PVT1 in human cancers.






Datum: 18.11.2017


Editorial board members

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474










Datum: 18.11.2017


Comparing the diagnostic ability of inflammatory markers in metabolic syndrome

Publication date: December 2017
Source:Clinica Chimica Acta, Volume 475

Author(s): Ge Meng, Qi Zhu, Junwei Shao, Qing Zhang, Li Liu, Hongmei Wu, Yang Xia, Xue Bao, Yeqing Gu, Honglei Wang, Hongbin Shi, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Guolin Wang, Kun Song, Yuntang Wu, Kaijun Niu

Background Chronic low-grade inflammation contributes to the pathogenesis of the metabolic syndrome (MetS). Although some studies have demonstrated that several standard inflammatory markers provide diagnostic value for MetS, few studies have compared the diagnostic ability of various inflammatory markers. We demonstrated the diagnostic ability of several inflammatory markers in detecting MetS. Methods Complement component 3 (C3), C4, high-sensitivity C-reactive protein (hs-CRP), leukocyte count, neutrophil, lymphocyte and neutrophil-to-lymphocyte ratio (NLR) concentrations were measured in 6312 participants living in Tianjin, China. MetS was defined according to American Heart Association criteria. Adjusted logistic models were used to assess associations between inflammatory markers and MetS. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic values of inflammatory markers for MetS. Results The adjusted odds ratio (95% CI) of MetS for the highest inflammatory markers (C3, leukocyte, neutrophil, lymphocyte) quintile, when compared to the lowest quintile were 2.68 (2.12–3.38), 2.53 (2.05–3.11), 1.31 (1.06–1.62) and 1.94 (1.60–2.37), respectively. ROC analysis showed that the optimal cut-off values were 101.0mg/dl for C3 (Area under the ROC curve (AUC)=0.68), 5.41×1000cells/mm3 for leukocyte (AUC=0.63), 3.20×1000cells/mm3 for neutrophil (AUC=0.60) and 1.82×1000cells/mm3 for lymphocyte (AUC=0.62). No significant association was observed between the other inflammatory markers and MetS. Conclusions Among the inflammatory markers assessed in this population, C3 has the strongest diagnostic value in detecting MetS. Further studies are encouraged to determine the efficacy of applying C3 to diagnosis and treatment in the clinical setting.






Datum: 18.11.2017


MicroRNA-10b and the clinical outcomes of various cancers: A systematic review and meta-analysis

Publication date: November 2017
Source:Clinica Chimica Acta, Volume 474

Author(s): Qiangxin Huang, Qian Song, Weixian Zhong, Yalan Chen, Ludong Liang

Background The impact of miR-10b expression on the survival outcome of patients with cancers is still controversial. Method and materials A systematic review and meta-analysis was performed to determine its implication on the survival of cancer patients. We carried out an electrical literature search to identify the eligible studies published in PubMed, Web of Science and Embase together with the Chinese databases. Result In total, 28 studies of 23 articles enrolling 3134 patients were included for this meta-analysis, of which 25 studies reported overall survival (OS), 4 studies evaluated recurrence-free survival (RFS) and 3 studies were related to disease-free survival (DFS). As a result, this meta-analysis revealed that up-regulation of miR-10b could confer an unfavorable factor for OS (HR=1.853, 95% CIs: 1.521–2.258, P <0.01) but not DFS (HR=1.309, 95% CIs: 0.699–2.453, P =0.4) or RFS (HR=2.692, 95% CIs: 0.877–8.265, P =0.084). Additionally, further analysis also suggested that overexpression of miR-10b predicted the shorter OS for the patient with different types of cancers, which contained lung cancer, breast cancer, glioma, colorectal cancer and gastric carcinoma. Subgroup analyses were also conducted according the region, sample size, system and miR-10b detection assay and statistical method. Conclusion This study shows that augmented expression of miR-10b strongly predicts poor prognosis for patients with cancers.






Datum: 18.11.2017






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