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  • Comparison of the time required for manual, visually read and semi-automated POCT urinalysis and pregnancy testing with associated electronic medical record (EMR) transcription errors
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-23
    Paul E. Young; Gabriel J. Diaz; Rinaben N. Kalariya; Peggy A. Mann; Maegan Benbrook; Kurosh R. Avandsalehi; John R. Petersen

    Background POCT urinalysis (UA) and urine pregnancy tests (UPT) are routinely performed in obstetrics and gynecology (Ob/Gyn) clinics by dipstick and pregnancy test kit methods respectively. In this study, we compared the time, efficiency and accuracy of these tests using manual, visually read methods and a semi-automated analyzer that was not interfaced to the EMR. Methods We prospectively enrolled 2525 patients at five Ob/Gyn clinics. Urine samples were tested using three different dipsticks for UA (2, 7 and 10 test pads) and the Sure-Vue™ urine pregnancy test kit. The samples were analyzed on the CLINITEK Status® Connect System and results compared for time taken and errors in results’ transcription. Results Using the CLINITEK Status Connect System, average test time and average total test time for UA dipsticks 7 and 10 test pads was significantly less than the manual, visually read method (0.77 and 0.64 minutes, respectively; p<0.001). The average test time for manual, visually read Chem 2 was significantly less than the CLINITEK Status Connect System (0.09 minutes; p=0.005), but not the average total test time (0.08 minutes; p=0.33). Average test time for a negative UPT using the CLINITEK Status Connect System was significantly greater (0.87 minutes; p<0.001). We found a transcription error rate of 0.3–1.7% for UA results and none for UPT. About 8% of UA and 12% of UPT results were not documented in EMR. Conclusion Performing the CLINITEK Status Connect System was more efficient than the manual, visually read process and if interfaced with the EMR would eliminate errors and non-documentation of results.

    更新日期:2020-01-23
  • RASSF1A: A promising target for the diagnosis and treatment of cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-23
    Yuling Bin; Yong Ding; Weisheng Xiao; Aijun Liao

    The Ras association domain family 1 isoform A (RASSF1A), a tumor suppressor, regulates several tumor-related signaling pathways and interferes with diverse cellular processes. RASSF1A is frequently demonstrated to be inactivated by hypermethylation in numerous types of solid cancers. It is also associated with lymph node metastasis, vascular invasion, and chemo-resistance. Therefore, reactivation of RASSF1A may be a viable strategy to block tumor progress and reverse drug resistance. In this review, we have summarized the clinical value of RASSF1A for screening, staging, and therapeutic management of human malignancies. We also highlighted the potential mechanism of RASSF1A in chemo-resistance, which may help identify novel drugs in the future.

    更新日期:2020-01-23
  • The exchangeable apolipoproteins in lipid metabolism and obesity
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-22
    Xin Su; Daoquan Peng

    Dyslipidemia, characterized by increased plasma levels of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and reduced plasma levels of high-density lipoprotein cholesterol (HDL-C), is confirmed as a hallmark of obesity and cardiovascular diseases (CVD), posing serious risks to the future health of humans. Thus, it is important to understand the molecular metabolism of dyslipidemia, which could help reduce the morbidity and mortality of obesity and CVD. Currently, several exchangeable apolipoproteins, such as apolipoprotein A1 (ApoA1), apolipoprotein A5 (ApoA5), apolipoprotein E (ApoE), and apolipoprotein C3 (ApoC3), have been verified to exert vital effects on modulating lipid metabolism and homeostasis both in plasma and in cells, which consequently affect dyslipidemia. In the present review, we summarize the findings of the effect of exchangeable apolipoproteins on affecting lipid metabolism in adipocytes and hepatocytes. Furthermore, we also provide new insights into the mechanisms by which the exchangeable apolipoproteins influence the pathogenesis of dyslipidemia and its related cardio-metabolic disorders.

    更新日期:2020-01-22
  • Long non-coding RNA TP73-AS1 in cancers
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Chao-Yang Gong; Rong Tang; Kai-Xing Liu; Gao Xiang; Hai-Hong Zhang

    More and more evidence indicates that long non-coding RNAs (lncRNAs), as a kind of non-coding endogenous single-stranded RNA, play an essential role as oncogenes or tumour suppressors in the occurrence and development of human cancers. The tumour protein P73 antisense RNA 1 (TP73-AS1) was initially found to be down-regulated in oligodendroglioma and may act as a non-protein-encoding RNA.Since its discovery, TP73-AS1 has been identified as a carcinogenic regulator of many malignancies. At the same time, the high expression of TP73-AS1 is related to the clinicopathological features of patients with cancer. It also regulates cell proliferation, anti-apoptosis, invasion and metastasis through a variety of potential mechanisms, suggesting that it may be a promising biomarker and therapeutic target for cancer. In this review, we summarize the biological functions, mechanisms, and potential clinical implications of TP73-AS1 dysregulation in tumourigenesis and progression.

    更新日期:2020-01-22
  • Decreased mitochondrial DNA copy number in children with cerebral palsy quantified by droplet digital PCR
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Bichao Lu; Fanyong Zeng; Wen Xing; Lin Liang; Jianbo Huo; Chianru Tan; Lingxiang Zhu; Zhizhong Liu

    Background Mitochondrial DNA copy number is a potential biomarker for mitochondrial dysfunction and is involved in a variety of disease states including autism, neurodegenerative diseases and traumatic brain injury, but few studies on mitochondrial DNA copy number in cerebral palsy have been reported. Therefore, this study aims to investigate the role of mitochondrial DNA copy number in children with cerebral palsy. Methods A total of 104 children with cerebral palsy and 78 typically developing children were enrolled in this study. All children with cerebral palsy were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. Mitochondrial DNA copy number was quantified by droplet digital PCR. Results We observed a significant reduction in mitochondrial DNA copy number from children with cerebral palsy comparing to healthy controls (216.76 ± 71.39 vs 359.66 ± 72.78, p < 0.001). An upward trend in mitochondrial DNA copy number alteration with the increase of age was found in healthy controls rather than in children with cerebral palsy. In addition, the mitochondrial DNA copy number in children with spastic hemiplegia was higher than that in children with spastic quadriplegia (152.27 ± 49.78 vs 90.64 ± 21.55, p = 0.001). Conclusions Our results suggest that on the basis of accurate quantification by droplet digital PCR, the declined mitochondrial DNA copy number probably has certain implications for mitochondrial dysfunction in children with cerebral palsy, which provides a new clue for the investigation on the molecular mechanism and clinical characteristics of cerebral palsy.

    更新日期:2020-01-22
  • Cell free DNA as a diagnostic and prognostic marker for cardiovascular diseases
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Iuliia A. Polina; Daria V. Ilatovskaya; Kristine Y. DeLeon-Pennell

    Release of cell free DNA (cfDNA) from damaged or dead cells routinely occurs in normal physiology. Recently, cfDNA has emerged as an essential biomarker in cardiovascular disease (CVD) of potential prognostic and diagnostic significance. Within the last decade, significant research efforts have been devoted to uncovering the mechanisms mediating cfDNA release and its outcome-predicting ability. The current review focuses on the pathways for cfDNA release in myocardial infarction, heart failure and hypertension, and discusses implementation of cfDNA monitoring to assess the overall development of these disease states and predict future complications.

    更新日期:2020-01-22
  • Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Kazuki Nakawatari; Makoto Kurano; Osamu Araki; Masako Nishikawa; Satoshi Shimamoto; Koji Igarashi; Junken Aoki; Masami Murakami; Yutaka Yatomi

    Objectives Although a single nucleotide polymorphism in a specific receptor for lysophosphatidylserine, a lysophospholipid mediator involved in the immune system, is reportedly associated with Graves’ disease, the association between lysophosphatidylserine and thyroid disorders remains to be elucidated. Therefore, we aimed to investigate the association between the level of phosphatidylserine-specific phospholipase A1 (PS-PLA1), which produces lysophosphatidylserine, and thyroid disorders. Methods We measured serum PS-PLA1 levels in the patients with various thyroid disorders (n = 120) and normal subjects (n =58). Results We observed that the serum PS-PLA1 levels were higher in the subjects with Graves’ disease, subacute thyroiditis, or silent thyroiditis, while they were not modulated in the patients with hypothyroidism. The serum PS-PLA1 levels were strongly correlated with the levels of thyroid hormones, especially in the subjects with Graves’ disease. Moreover, we found that the serum PS-PLA1 levels were lowered by treatment with anti-thyroid reagents in subjects with Graves’ disease and that the changes in PS-PLA1 were strongly correlated with those in thyroid hormones. Conclusion These results suggest that PS-PLA1 might be a novel target in the treatment of hyperthyroidism, especially Graves’ disease, and that its measurement might be useful as a supplementary diagnostic test for thyroid function.

    更新日期:2020-01-22
  • Evaluation of a panel of very long-chain lysophosphatidylcholines and acylcarnitines for screening of X-linked adrenoleukodystrophy in China
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Guo-Li Tian; Feng Xu; Kuan Jiang; Yan-Min Wang; Wei Ji; Ying-Ping Zhuang

    Background Elevated blood C24:0- and C26:0-carnitines and lysophosphatidylcholines (LPCs) were reported as diagnostic biomarkers for X-linked adrenoleukodystrophy (X-ALD). Our aim was to establish the reference intervals of very long-chain (VLC) acylcarnitines (C20-C26) and LPCs in Chinese population, and evaluate valuable biomarkers and develop panel for screening X-ALD in China. Methods The method of FIA-MS/MS–based quantification of VLC acylcarnitines and LPCs was validated in order to determine their concentrations in dried blood spots from 7 X-ALD boys, 396 age-matched healthy controls, and 3078 putative normal newborns. Screening performance of these metabolites for X-ALD was clinically evaluated. Results The reference intervals of VLC acylcarnitines, LPCs and their ratios were established in Chinese population, and for some metabolites like C26 and C26:0-LPC, the reference intervals were found to be significantly different between children and newborns. C24 and C26, C26:0-LPC, C24/C22 and C26/C22 ratios were found to have better performance than other analytes to identify X-ALD boys from normal children. Conclusion C26:0-LPC, C24 and C26 are three most valuable biomarkers for screening of X-ALD in children group. The information of age-related variations in concentration of some biomarkers is helpful for accurate screening of X-ALD.

    更新日期:2020-01-22
  • Biotin interferences: Have we neglected the impact on serological markers?
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Jean-Louis Bayart; Julien Favresse; Anke Stoefs; Mélanie Closset; Tatiana Roy; Catherine Fillée; Hector Rodriguez-Villalobos; Benoît Kabamba-Mukadi; Damien Gruson

    Background Biotin has been reported to be a leading cause of interference on several immunoassay platforms using the streptavidin-biotin immobilization system. While biotin interferences have now been well characterized for several assays, only few data are available on their impact on serological markers of infectious viral diseases. Methods Overall, 10 healthy volunteers (HVs) received a single 100mg dose of biotin to evaluate its effect on hepatitis B serological markers. Blood samples were taken several times before and after biotin intake. In addition, spiking experiments were applied to investigate biotin’s impact on anti-HIV/p24 Ag and anti-HCV antibody levels. Several procedures designed to overcome this interference were evaluated. Results Biotin intake resulted in a false-negative anti-HBs immunological status (<10 mIU/mL) in 40.0% of cases. According to our anti-HBc and anti-HBe results, biotin intake was associated with 90.0% and 80.0% of false positive results, respectively. At the theoretical biotin peak concentration following a 100mg intake, 50.0% and 66.6% of anti-HIV and anti-HCV results were false negatives, respectively. All the procedures evaluated to overcome the interference were proven effective. Conclusion HBV, HCV, and HIV serological markers are likely to be highly sensitive to biotin. Our data confirm that the scope of biotin interference is broader than commonly described.

    更新日期:2020-01-22
  • Association of Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, and Coronary Plaque Properties: An Optical Coherence Tomography-based Observational Study
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-21
    Toshihiko Oshita; Ryuji Toh; Yuichiro Nagano; Koji Kuroda; Yoshinori Nagasawa; Amane Harada; Katsuhiro Murakami; Maria Kiriyama; Keiko Yoshikawa; Keiko Miwa; Takuya Kubo; Takuya Iino; Manabu Nagao; Yasuhiro Irino; Tetsuya Hara; Masakazu Shinohara; Hiromasa Otake; Toshiro Shinke; Ken-ichi Hirata

    Background Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as “cholesterol uptake capacity (CUC)”. Objective To clarify the cross-sectional relationship between CUC and coronary plaque properties. Methods We enrolled 135 patients to measure CUC and assess the morphological features of angiographic stenosis by optical coherence tomography (OCT). We estimated the extent of the lipid-rich plaque by multiplying the mean lipid arc by lipid length (lipid index). The extent of the OCT-detected macrophage accumulation in the target plaque was semi-quantitatively estimated using a grading system. Results Lipid-rich plaque lesions were identified in 125 patients (92.6%). CUC was inversely associated with the lipid index (R = −0.348, P < 0.0001). In addition, CUC was also inversely associated with macrophage score (R = -0.327, P < 0.0001). Conversely, neither circulating levels of HDL cholesterol nor apoA1 showed a similar relationship. Conclusions We demonstrated that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation, suggesting that CUC could be useful for cardiovascular risk stratification.

    更新日期:2020-01-21
  • Fecal microbiota transplantation in disease therapy
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-20
    Hanna Antushevich

    Fecal microbiota transplantation (FMT) is the introduction (transplantation) of gut microbiota obtained from the faeces of a healthy donor into the patient’s gastrointestinal tract. Most often, such therapy is used the treatment of gastrointestinal diseases caused by the activity of pathogenic or conditionally pathogenic microorganisms, however, recently an increasing number of studies have reported the use of fecal microbiota transplantation for the treatment of diseases such as metabolic syndrome, diabetes, cancer and Parkinson's disease. This review article presents the results of studies concerning the impact of FMT on weight gain, immunological response and the treatment of neurological and gastrointestinal diseases and cancer. The procedure of fecal microbiota transplantation and possible side effects that may appear in FMT recipients are also described.

    更新日期:2020-01-21
  • A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-18
    Guodong Zhao; Yong Ma; Hui Li; Shiming Li; Yun Zhu; Xiaoyu Liu; Shangmin Xiong; Yi Liu; Jin Miao; Sujuan Fei; Minxue Zheng; Xiangwei Zhao

    Background Methylated SFRP2 was previously reported as a non-invasive biomarker for colorectal cancer (CRC) detection with a relatively low sensitivity for early stage CRC. The purpose of this study was to evaluate the performance of a new plasma based CRC screening assay, SpecColon test, which tested methylated SFRP2 and SDC2 simultaneously in a single qPCR reaction, in detecting CRC and advanced adenomas (AA). Method One milliliter plasma of 122 CRC patients, 12 AA patients, 93 patients with benign polyps, and 91 normal individuals were collected from the Affiliated Hospital of Xuzhou Medical University, and all samples were examined by SpecColon test. Results The sensitivities for detecting AA and CRC by methylated SFRP2 alone were 50.0% (95% CI: 22.2 – 77.7%) and 63.1% (95% CI: 53.9 – 71.5%) with a specificity of 90.1% (95% CI: 81.6 – 95.1%). The sensitivities by methylated SDC2 alone were 33.3% (95% CI: 11.3 – 64.6%) and 56.6% (95% CI: 47.3 – 65.4%) with a specificity of 95.6% (95% CI: 88.5 – 98.6%). However, when methylated SFRP2 and methylated SDC2 were combined, the sensitivities for AA and CRC detection improved to 58.3% (95% CI: 28.6 – 83.5%) and 76.2% (95% CI: 67.5 – 83.3%) with a specificity of 87.9% (95% CI: 79.0 – 93.5%). The positive detection rates of benign polyp group and normal control group showed no significant difference (p>0.01), whereas AA and CRC groups had significantly higher positive detection rates than normal individual group (p<0.001). Conclusion The sensitivities for AA and early stage CRC by combined test of methylated SFRP2 and methylated SDC2, the so called SpecColon test, improved upon those by either biomarker alone without significant impact on the specificity. It has the potential to become a powerful, convenient and highly effective screening tool for early CRC screening.

    更新日期:2020-01-21
  • Genetic and functional analysis of two missense mutations in CD46 predispose to postpartum atypical hemolytic uremic syndrome
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-13
    Hao Wu; Zhaomin Mao; Ying Tan; Yanfang Jiang; Jinyu Yu; Li Song; Shan Wu; Mindan Sun; Li Zhu; Xiaojuan Yu; Li Zhang; Feng Yu; Ming-hui Zhao

    Pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) is a disease with a triad of hemolytic anemia, thrombocytopenia and acute renal failure, which might be attributed to the uncontrolled complement activation. Herein, we sequenced a postpartum-aHUS patient and found the two missense variants of CD46, a novel mutation (c.403G>C, p.G135R) from her father and a once reported mutation (c.293C>T, p.T98I) without expressional and functional tests from her mother. The G135R mutation caused a significantly reduced membrane expression of CD46 in peripheral blood lymphocyte and renal cells. The T98I mutation caused a mild decrease membrane expression of CD46 in peripheral blood lymphocyte cells. Moreover, the expressed G135R protein was in precursor form, indicating that this mutant was retained intracellularly. The C3b binding ability of T98I mutant was slightly decreased while the C4b binding ability is not significantly changed. The cofactor ability of the two mutants for factor I in the degradation of C3b was demonstrated to be impaired. This study reported the first case of a four-generation postpartum-aHUS pedigree with isolated CD46 variants and the detailed disease progression, treatment, and prognosis provided more meaningful information for the understanding the disease.

    更新日期:2020-01-14
  • Autophagy in chronic stress induced atherosclerosis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-13
    Na Li; Ru-Xin Zhang; Xue-Jiao Xie; Hong-Feng Gu

    Atherosclerosis, a complex multifactorial disease, is the leading cause of acute cardiovascular events. Substantial evidence confirms that chronic stress plays a pivot role in the occurrence and development of atherosclerosis, but the specific mechanism remains unclear. Autophagy serves as a safeguard mechanism for sustaining cellular homeostasis via eliminating unnecessary or/and harmful components, and damaged organelles in response to various stress. An increasing number of studies indicate that autophagy plays vital roles in the development of atherosclerosis. Therefore, understanding the role of chronic stress in the regulation of autophagy may provide new insight into prevention and treatment atherosclerotic disease, especially with respect to emerging targeted therapy. In present review, we focus on changes in autophagic function under chronic stress and its relationship to atherosclerosis.

    更新日期:2020-01-13
  • The role of IL-1β in aortic aneurysm
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-13
    Fan Wenjing; Tang Tingting; Zeng Qian; Wan Hengquan; Zhao Simin; Oware Kwabena Agyare; Jiang Zhisheng; Qu Shunlin

    Interleukin-1β (IL-1β) is a vital cytokine that plays an important role in regulating immune responses to infectious challenges and sterile insults. In addition, two endogenous inhibitors of functional receptor binding, IL-1 receptor antagonist (IL-1Ra), complete the family. To gain biological activity, IL-1β requires processing by the protease caspase-1 and activation of inflammasomes. Numerous clinical association studies and experimental approaches have implicated members of the IL-1 family, their receptors, or components of the processing machinery in the underlying processes of cardiovascular diseases. Here, we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in aneurysm. We discuss clinical evidence, signalling pathway, and mechanism of action and last, lend a perspective on currently developing therapeutic strategies involving IL-1β in aneurysm.

    更新日期:2020-01-13
  • Long non-coding RNA in bladder cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-12
    Yuepeng Cao; Tian Tian; Weijian Li; Hanzi Xu; Chuanfei Zhan; Xuhong Wu; Chao Wang; Xiaoli Wu; Wanke Wu; Shuyun Zheng; Kaipeng Xie

    Bladder cancer (BC) is the ninth most common malignant disease and ranks fourteenth in cancer mortality worldwide. Moreover, among cancers, the incidence and mortality of BC in males increased to the 6th and 9th place, respectively. The overall survival (OS) declines dramatically as the cancer progresses, especially when urothelial cells transition from noninvasive to invasive. It is well known that epithelial cells can acquire invasive properties and a propensity to metastasize through the epithelial-to-mesenchymal transition (EMT) process in tumourigenesis and progression. However, the potential molecular mechanisms and key pathways are still unclear. As the sequencing technology advances, long non-coding RNAs (lncRNAs) have been proven to play an important role in regulating biological processes and cellular pathways. Here, we reviewed important lncRNAs, such as H19, UCA1 and MALAT1, that participate in the malignant phenotype of BC and regulate EMT signalling networks in the invasion-metastasis cascade during BC development. We further discuss MALAT1, PCAT-1 and SPRY4-IT1, and also urine and blood exosomal H19 and PTENP as potential noninvasive biomarkers. Moreover, antisense oligonucleotides (ASOs) and a double-stranded DNA plasmid (BC-819) have been designed for use in preclinical cancer models and clinical trials in patients. Therefore, the results of investigations have gradually prompted the utility of lncRNAs.

    更新日期:2020-01-13
  • Effect of vitamin D supplementation on clinical outcome and biochemical profile in South Indian population with vitamin D-deficient chronic urticaria- a randomized double-blind placebo controlled trial
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-09
    Archana Mony; Laxmisha Chandrashekar; Medha Rajappa; Malathi Munisamy; Jaya Prakash Sahoo; Sandhiya Selvarajan

    Background Chronic urticaria (CU) is a debilitating inflammatory skin disease. Prior studies have shown reduced concentrations of vitamin D in CU and there are limited reports of potential beneficial role for vitamin D supplementation in the treatment of subjects with CU. We assessed the effect of vitamin D supplementation in vitamin D deficient CU patients on the clinical outcome and inflammatory markers in South Indian patients with CU. Methods This randomized controlled trial involved 120 vitamin-D deficient CU patients. Urticaria activity score (UAS7) and autologous plasma skin test (APST) status was assessed in all cases. CU patients were supplemented with vitamin D with a dose of 60,000 IU fortnightly for a period of 12 weeks and those in the placebo arm received matched placebo. Five milliliters of blood was drawn from all study subjects at baseline and after 12 weeks for assessing inflammatory markers. Results We observed a significant reduction in UAS7 scores after 12 weeks in the vitamin D treated group in comparison to that of placebo. We also noted a significant reduction of the inflammatory cytokines in the vitamin D treated group. Conclusion Supplementation with vitamin D among patients with vitamin D deficient CU significantly decreases disease severity which is probably mediated through reduction of systemic inflammation.

    更新日期:2020-01-09
  • Serum uric acid to lymphocyte ratio: a novel prognostic biomarker for surgically resected early-stage lung cancer. A propensity score matching analysis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-09
    Zhang Yang; Shuangjiang Li; Liang Zhao; Wenyu Lv; Juan Ju; Wenbiao Zhang; Jue Li; Guowei Che

    Backgrounds This study aims to evaluate the prognostic impact of serum uric acid to lymphocyte ratio (ULR) in video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small-cell lung cancer (NSCLC) through a propensity score-matching (PSM) analysis. Methods This study was carried out based on a prospectively-maintained database in our institution between January 2014 and July 2015. Survival analysis using a log-rank test was performed to distinguish the differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified according to an optimal cut-point of ULR. Finally, multivariable Cox proportional hazards regression analysis and PSM analysis were conducted to identify the prognostic factors of NSCLC. Results There were 335 patients with surgically resected primary stage I-II NSCLC included. An ULR at 3.83 was found to be the optimal cut-point regarding postoperative survival. Both OS and DFS of the patients with ULR>3.83 were significantly shortened compared to those of the patient with ULR≤3.83. Patients with ULR>3.83 had significantly lower rates of OS and DFS until the last follow-up date than those of patients with ULR≤3.83. These differences still remained significant after PSM analysis. Multivariate analyses for the entire cohort finally demonstrated that an elevated ULR could independently predict both unfavorable OS and DFS of surgically resected stage I-II NSCLC. Conclusions ULR can be considered as a novel risk stratification tool to refine prognostic prediction for operable early-stage NSCLC.

    更新日期:2020-01-09
  • Diagnostic value of quantitative MP-IgG for Mycoplasma pneumoniae pneumonia in adults
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-09
    Lina Wu; Maosheng Ye; Xiaosong Qin; Yong Liu; Zhe Lv; Rui Zheng

    The passive particle agglutination (PA) test, once widely used for Mycoplasma pneumoniae (M. pneumoniae) antibody detection, has gradually been replaced by quantitative enzyme-linked immunosorbent assays (ELISA). However, the lack of diagnostic criteria for quantitative ELISA M. pneumoniae-IgG(MP-IgG) and the low positive rates of ELISA M. pneumoniae-IgM (MP-IgM) limit the diagnostic value of ELISA for M. pneumoniae infection in adults. Here, the diagnostic value of quantitative ELISA MP-IgG was evaluated in adults with Mycoplasma pneumoniae pneumonia (MPP). The serum M. pneumoniae antibodies were detected in 162 patients with MPP, 228 patients with community-acquired pneumonia (CAP) with non-Mycoplasma pneumoniae(NMP), and 162 healthy controls by ELISA, using the PA results as the reference standards. For the MP-IgM-/IgG+ subgroup, a single serum MP-IgG level of ≥92.67 RU/mL can be used as a reference criterion for the diagnosis of acute M. pneumoniae infection. At admission, for patients with CAP, the sensitivity and specificity of ELISA MP-IgM positivity for MPP were 18.51% and 99.56%, respectively. MP-IgM positivity combined with MP-IgG ≥92.67 RU/mL increased the sensitivity to 40.12% and decreased the specificity to 94.29%. For paired serum samples obtained within seven days, an ELISA MP-IgG concentration change of ≥ 1.48-fold and MP-IgG ≥ 92.67 RU/mL on day 7 were used as the diagnostic criteria for M. pneumoniae infection. Accordingly, the combination of qualitative MP-IgM detection and quantitative MP-IgG detection by ELISA is valuable for acute MPP diagnosis in adults.

    更新日期:2020-01-09
  • Circulating miR-214-3p predicts nasopharyngeal carcinoma recurrence or metastasis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-08
    Jianfeng Wang; Yi Xu; Jiyun Wang; Haiyue Ying

    Background Due to the remarkably stable form in the bloodstream, circulating microRNAs (miRNAs) are indicated as promising novel minimally invasive biomarkers in many cancers. However, available data of miRNAs in nasopharyngeal carcinoma (NPC) are relatively limited. Methods Based on the GEO database and previous published reports, 21 dysregulated miRNAs were selected for screening via microarray analysis (20 NPC samples vs 10 controls). Dysregulated miRNAs were then detected and verified by the method of quantitative reverse transcription–polymerase chain reaction (qRT-PCR) in the training and validation sets. The candidate miR-214-3p was then evaluated in the evaluation set, including the association between miR-214-3p and clinicopathological characteristics, dynamic changes in NPC patients and the predictive value for NPC recurrence or metastasis. Results Seven miRNAs were significantly altered in comparison with healthy controls by microarray analysis. MiR-214-3p was the most significantly expressed in training and validation sets by qRT-PCR. Plasma miR-214-3p expressions were significantly associated with UICC stages and NPC recurrence or metastasis. Plasma miR-214-3p expressions showed a gradual decrease during the follow-up after treatment in NPC patients. Patients with recurrence or metastasis were always accompanied with higher levels of plasma miR-214-3p at the same time point. High pretreatment miR-214-3p expression (≥3.12) was significantly associated with NPC recurrence or metastasis by log-rank test using Kaplan-Meier survival curve analysis (P=0.006). Conclusions Circulating miR-214-3p can serve as a noninvasive biomarker for the prediction of recurrence or metastasis in NPC patients.

    更新日期:2020-01-08
  • Triglyceride metabolism and angiopoietin-like proteins in lipoprotein lipase regulation
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-07
    Jing Li; Liang Li; DongMing Guo; SuYun Li; YuXin Zeng; ChuHao Liu; Ru Fu; MengQian Huang; Wei Xie

    Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family, especially ANGPTL3, ANGPTL4 and ANGPTL8, which regulate lipoprotein lipase (LPL) activity, play pivotal roles in triglyceride (TG) metabolism and related diseases/complications. There are many transcriptional and post-transcriptional factors that participate in physiological and pathological regulation of ANGPTLs to affect triglyceride metabolism. This review is intended to focus on the similarity and difference in the expression, structural features, regulation profile of the three ANGPTLs and inhibitory models for LPL. Description of the regulatory factors of ANGPTLs and the properties in regulating the lipid metabolism involved in the underlying mechanisms in pathological effects on diseases will provide potential therapeutic approaches for the treatment of dyslipidemia related diseases.

    更新日期:2020-01-07
  • Immunological role and underlying mechanisms of B7‐H6 in tumorigenesis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2020-01-03
    Yuxuan Hu; Tian Zeng; Zheng Xiao; Qihao Hu; Yukun Li; Xiongjin Tan; Haiyan Yue; Wensong Wang; Hui Tan; Juan Zou

    B7 homolog 6 (B7‐H6) has been identified as involved in tumorigenesis. Elucidating its role and potential mechanism of action is essential for understanding tumorigenesis and the potential development of an effective clinical strategy. Abnormal overexpression of B7‐H6 in various types of tumors was reported to be linked with poor prognosis. B7‐H6 suppresses the initiation of the “caspase cascade” and induces anti-apoptosis by STAT3 pathway activation to provoke tumorigenesis. B7‐H6 facilitates tumor proliferation and cell cycle progression by regulating apoptosis suppressors. B7‐H6 induces cellular cytotoxicity, secretion of TNF-α and IFN-γ and B7-H6-specific BiTE triggers T cells to accelerate tumorigenesis. B7‐H6 induces abnormal immunological progression by HER2-scFv mediated ADCC and NKp30 immune escape to promote tumorigenesis. B7‐H6 promotes tumorigenesis via apoptosis inhibition, proliferation and immunological progression. B7‐H6 may a valuable potential biomarker and therapeutic strategy for diagnostics, prognostics and treatment in cancer.

    更新日期:2020-01-04
  • Screening and Analysis of Small Molecular Peptides in Urine of Gestational Diabetes Mellitus
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-31
    Zhiying Hu; Man Zhang; Yaping Tian

    Gestational diabetes mellitus (GDM) is a common clinical disease with complicated clinical process and harmful effects on pregnant women and fetus. The purpose of this study is to use the convenient urine samples in combination with glucose levels to detect or predict GDM. In this study, urine samples of non-pregnant women, normal pregnant women and GDM patients were collected. The peptides in urine were enriched by weak cationic exchange magnetic beads (MB-WCX) and analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). 46 polypeptide peaks with statistical difference (P < 0.01) were screened out by using Bioexplorer analysis software. The level of molecules with mass-to-charge ratio of 1079.2, 1290.6 and 1500.7 was higher in the GDM group than the other two groups. Through the analysis of differential molecules by liquid chromatography tandem mass spectrometry (LC-MS), the above molecules were identified as coagulation factor IX, TBC1 family member 5 isoform a [Homo sapiens] (TBC1D5a) and immunoglobulin kappa constant. The discovery of polypeptides provides the research basis for further primary screening and assistant diagnosis of GDM through urine samples.

    更新日期:2020-01-01
  • Acid-sensing ion channels: linking extracellular acidification with atherosclerosis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-31
    Rong-Jie Zhang; Yu-Fang Yin; Xue-Jiao Xie; Hong-Feng Gu

    Extracellular acidification in atherosclerosis-prone regions of arterial walls is considered pro-atherosclerotic by exerting detrimental effect on macrophages, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Acid-sensing ion channels (ASICs), a family of extracellular H+ (proton)-gated cation channels, are present extensively in the nervous system and other tissues, implying physiologic as well as pathophysiologic importance. Aberrant activation of ASICs is thought to be associated in EC dysfunction, macrophage phenotypic switch, and VSMC migration and proliferation. Although in vitro evidence acknowledges the contribution of ASIC activation in atherosclerosis, no direct evidence confirms their pro-atherosclerotic roles in vivo. In this review, the effect of extracellular acidity on three major contributors, ECs, macrophages, and VSMCs, is discussed focusing on the potential roles of ASICs in atherosclerotic development and underlying pathology. A more comprehensive understanding of ASICs in these processes may provide promising new therapeutic targets for treatment and prevention of atherosclerotic diseases.

    更新日期:2019-12-31
  • HOTAIR LncRNA: A novel oncogenic propellant in human cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-31
    Taruna Rajagopal; Srikanth Talluri; R.L. Akshaya; Nageswara Rao Dunna

    Long non-coding RNAs (lncRNAs) are an important novel class of non-coding RNAs having lengths of 200 nucleotides and low expression. The HOX Transcript Antisense Intergenic RNA (HOTAIR) is one of the most extensively studied lncRNAs found dysregulated in human cancer. Although a growing body of evidence suggests a role fo HOTAIR in pathogenesis, disease progression, drug resistance and reduced survival, its mechanism of action remains largely unclear. Recent studies have identified that HOTAIR facilitates protein-protein interaction thereby affecting diverse pathways in cancer such as epigenetic reprogramming, protein stability and signal transduction. HOTAIR has been shown to promote tumor progression by regulating microRNA expression and function. Moreover, several HOTAIR gene variants have recently been identified and found to increase cancer susceptibility. Here we review recent data on the critical role of HOTAIR in human malignancy and its potential mechanism of action. A more comprehensive understanding of this unique lncRNA is critical to elucidating the pro-oncogenic function of HOTAIR its potential application in diagnosis, prognosis and treatment.

    更新日期:2019-12-31
  • Diverse roles of SNHG16 in Human Cancers
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-31
    Chao-Yang Gong; Hai-Hong Zhang

    In recent years,more and more evidence shows that long non-coding RNAs (lncRNAs), as a novel class of non-coding endogenous single-stranded RNA, play a key role in multiple physiological and pathological processes through transcriptional interference, post-transcriptional regulation and epigenetic modification. Meanwhile, many studies have shown that lncRNAs, as oncogenes or tumor suppressors,play an important role in the occurrence and development of human cancers. Small nucleolar RNA host gene 16 (SNHG16) was initially identified as an oncogenic long non-coding RNA in neuroblastoma. Since its discovery, SNHG16 has been identified as a carcinogenic regulator of various malignant tumors. Meanwhile, the high expression of SNHG16 is related to the clinical and pathological characteristics of cancer patients, and regulates cell proliferation, apoptosis, invasion and metastasis through a variety of potential mechanisms. These evidences indicates that SNHG16 may be a promising biomarker and therapeutic target for cancers. In this review, we summarized the biological function, related mechanism and potential clinical significance of SNHG16 in multiple human cancers.

    更新日期:2019-12-31
  • Emerging biomarkers in Multiple Myeloma: A Review
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-31
    Nidhi Gupta; Aparna Sharma; Alpana Sharma

    Multiple myeloma (MM) is the second most common hematological malignancy after non-Hodgkin lymphoma and is manifested by uncontrolled proliferation and accumulation of abnormal plasma cells in the bone marrow (BM). The incidence along with deaths associated with MM is on rise due to lack of an effective diagnosis at an early stage. The identification of MM decades ago marks the adoption of certain conventional markers such as plasma cell percentage in BM, serum protein electrophoresis for M-band and urinary Bence-Jones protein. This was then followed by utilization of β2 microglobulin and serum albumin for determining the staging of MM. The need for a better diagnostic or prognostic marker prompts researchers and hence, certain novel markers have been tested which includes extracellular matrix proteins, angiogenic factors, telomeres and telomerase along with the immune markers. Nowadays, proteomic and genomic studies are being performed to identify novel diagnostic and/or prognostic markers for MM. Followed by this, comes the emerging concept of liquid biopsy which allows easy and non-invasive detection of the disease. The liquid biopsy comprises of circulatory tumor cells along with the nucleic acids (microRNAs and cell-free DNA) released from the tumor cells in peripheral circulation which could be a true representation of BM. This review, hence, summarizes the emerging biomarkers involved in the diagnosis and prognosis of MM.

    更新日期:2019-12-31
  • Combinations of exonic deletions and rare mutations lead to misdiagnosis of propionic acidemia
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-29
    Handuo Wang; Lanlan Meng; Wen Li; Juan Du; Yueqiu Tan; Fei Gong; Guangxiu Lu; Ge Lin; Qianjun Zhang

    Propionic acidemia (PA) is an inborn metabolic error characterized by the accumulation of propionic acid due to deficiency of propionyl-CoA carboxylase (PCC). In this study, we present an intractable case with PCC activity defects. Although next-generation sequencing was applied twice to test genetic defects of the patients, no pathogenic mutations of a metabolic disease gene were identified. Mutations related to the disease were screened in prenatal diagnosis, but the mother still gave birth to an unhealthy neonate. We analyzed the second sequencing data and found that a novel synonymous PCCA mutation c.1746 G>C (p.S582S), which leads to an exon 19 skip, was screened out. Furthermore, a deletion mutation covering exon 3 and exon 4 of the PCCA gene was identified using q-PCR and DNA breakpoint test. Both of these can result in the loss of PCCA protein function. The finding expands the mutation spectrum of the PCCA gene and indicates that another technology such as cDNA analysis, multiplex ligation-dependent probe amplification (MLPA), or long-read whole-genome sequencing should be considered to improve the detection rates of special cases.

    更新日期:2019-12-29
  • Newborn Screening and Diagnosis of Inborn Errors of Metabolism: A 5-year Study in An Eastern Chinese Population
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-29
    Chiju Yang; Cheng Zhou; Peng Xu; Xianlian Jin; Wenhua Liu; Wenjun Wang; Chenggang Huang; Mengyi Jiang; Xigui Chen

    Inborn errors of metabolism (IEMs) can cause intellectual disability or even death in children. To evaluate the disease spectrum and genetic characteristics of IEMs in Jining City of Shandong Province in East China, we used tandem mass spectrometry (MS/MS) technology for IEM screening combined with genetic analysis. Newborns were screened from July 14, 2014, to December 31, 2018. Amino acid and carnitine contents were detected by MS/MS. According to the results for normal newborns, the reference range of our laboratory was established with the percentile method. The suspected positive newborns were further diagnosed using next-generation sequencing. A total of 514,234 newborns were screened, and 265 were diagnosed with IEMs, with a detection rate of 1:1941. Of the 265 patients, 130 (49.06%) had organic acid disorders, 83 (31.32%) had amino acid disorders, 34 (12.83%) had fatty acid oxidation disorders, and 18 (6.79%) had urea circulatory disorders. PAHD and MMA were the two most common disorders. IEM-associated genes were identified in 233 patients. Our data indicated that IEMs are never uncommon in Jining, and the disease spectrum and genetic background were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in the region.

    更新日期:2019-12-29
  • Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-28
    Zhen Xun; Can Liu; Qing-Qing Yu; Jin-Piao Lin; Jin-Lan Huang; Ting-Wen Yang; Wen-Nan Wu; Song-Hang Wu; Qi-Shui Ou

    Background and Aim Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. Methods The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. Results ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. Conclusions ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

    更新日期:2019-12-29
  • A Thin-Film Interferometry-Based Label-Free Immunoassay for the Detection of Daratumumab Interference in Serum Protein Electrophoresis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-26
    Yiqi Ruben Luo; Indrani Chakraborty; Robert F. Zuk; Kara L. Lynch; Alan H.B. Wu

    Background Daratumumab (DARA) is a fully human anti-CD38 IgG1-κ monoclonal antibody drug used in the treatment of multiple myeloma (MM). While serum protein electrophoresis (SPEP) is an important assay for diagnosis and monitoring of patients with MM, DARA can appear in the γ-region as a single band and interfere with the interpretation of SPEP results. An approach to detect the interference is measuring the quantity of DARA in serum samples and assessing its impact on SPEP results. Immunoassays based on label-free technologies, i.e. label-free immunoassays (LFIA’s), can achieve real-time immunometric measurement without attaching a reporter molecule (enzyme, fluorophore, etc.) to the immunocomplex. The recorded time course of the immunocomplex formation allows for quantitation on initial binding rate, which facilitates rapid measurement within a few minutes. Based on the thin-film interferometry (TFI) technology, a rapid LFIA was established for the quantitation of DARA in serum samples. Methods The TFI-based LFIA for DARA was validated for imprecision (CV), accuracy, limit of quantitation (LOQ), and analytical measurement range (AMR). Interference to the LFIA was evaluated using a group of protein samples, as well as hemolytic, lipemic, and icteric clinical samples. Results The precision of the TFI-based LFIA’s for DARA ranged from 6.5% to 10.7% (within-run CV), and 7.4% to 11.6% (between-run CV), with a bias of -2.1% to 10.1%. The LOQ was 10 μg/ml (n = 4, CV 9.8%), with an AMR ranging from the LOQ to 1000 μg/ml. The LFIA was used to measure 37 patient samples submitted for SPEP testing. The LFIA results were 100% consistent with the history of DARA use as documented in the medical record. Conclusions The TFI-based LFIA was successful at accurately identifying DARA in serum samples and can be used to identify DARA interference in SPEP testing. This work demonstrates the applicability of label-free technologies, particularly the TFI technology, to clinical diagnostic needs. Given the simplicity and the speed of the testing process, the TFI technology provides a unique testing approach for the measurement of proteins in clinical samples.

    更新日期:2019-12-27
  • Same-sex twins have a high incidence of congenital hypothyroidism and a high probability to be missed at newborn screening
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-23
    Xiang Jiang; Yong-lan Huang; Yi Feng; Fang Tang; Xue-fang Jia; Qian-yu Chen; Cheng-fang Tang; Si-chi Liu; Bei Li; Rui-dan Zheng; Ji-lian Liu

    Background We estimated the incidence of CH in twins, analyse the clinical features of CH cases in twins and further evaluate the CH screening strategy and recall procedures for twins. Methods A retrospective investigation of the screening results and confirmed cases in 724,791 newborns was conducted from 2015 to 2017 in Guangzhou. Clinical features were compared between twins with CH and singletons with CH. In addition, the twins were further divided into same-sex twins and different-sex twins to analyse the characteristics and incidence of CH and to compare differences in the confirmed cases in the 2 groups. Results The incidence of CH in same-sex twins was 1/593, which was much higher than the incidence of CH in singletons (1/1323) and different-sex twins (1/3060). Of the 20 twins diagnosed with CH, 17 were same-sex twins and 3 were different-sex twins. Among the six pairs of same-sex twins with CH, four had TSH inconsistency, which reached 67%. Eight of the 17 cases of same-sex twins diagnosed with CH had negative results at the first screening. Conclusions Distinguishing same-sex twins from different-sex twins during newborn screening is more feasible. The incidence of CH in same-sex twins is much higher than that in the general population and the risk of transient CH is relatively high. In positive cases in same-sex twins, the simultaneous recall of the twin can effectively avoid a missed diagnosis. The screening center should properly evaluate the recall strategy and screening procedure for twins, especially twins of the same-sex.

    更新日期:2019-12-23
  • The Rare Alus Element-mediated Chimerism of Multiple de novo Complex Rearrangement Sequences in GAN Result in Giant Axonal Neuropathy
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-23
    Meizhen Shi; Xin Chen; Lanlan Zeng; Zhuo Li; Desheng Liang; Lingqian Wu

    Giant axonal neuropathy (GAN) is a rare and grievous autosomal recessive neurodegenerative disease due to loss-of-function mutation in GAN. However, the chimerism of complex rearrangement sequences of GAN has not been reported so far, and the mechanism for its complex rearrangements remains to be determined. We identified a family with clinical symptoms of GAN and aimed to reveal a genetic cause underlying this disease. By whole-exome sequencing in the patient we identified a novel homozygous frameshift mutation with 1bp deletion (c.27delC) in GAN. However, when analyzed the patient’s genomic DNA (gDNA) by quantitative real-time PCR and breakpoint DNA sequencing, we found the chimerism of multiple complex rearrangement sequences encompassing exon 1 of GAN in the patient's genome. The microhomology and localization of the breakpoint indicated that they may be caused by Alu repeat elements. We also found that the mRNA expression level of GAN in patient’s lymphocyte was decreased, confirming the pathogenicity of these mutations. Our study is the first reported on many complex rearrangement sequences mosaic in GAN mediated by Alu element. The patient here is not a simple homozygous frameshift mutation, but a compound heterozygous paternal c.27delC mutation and the chimerism of multiple de novo complex rearrangement sequences in GAN. Our results may also provide new insights into the formation and pathogenicity of complex rearrangement in GAN, and may be helpful to genetic counseling and genetic testing. It also enriches the Alu-mediated disease-associated database which are important for correct clinical interpretation.

    更新日期:2019-12-23
  • Autophagy, an important therapeutic target for pulmonary fibrosis diseases
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-23
    Hong Zhao; Yiqun Wang; Tingting Qiu; Wei Liu; Pingbo Yao

    As an evolutionarily conserved intracellular degradation pathway, autophagy is essential to cellular homeostasis. Several studies have demonstrated that autophagy showed an important effect on some pulmonary fibrosis diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis lung disease, silicosis and smoking-induced pulmonary fibrosis. For example, autophagy mitigates the pathological progression of IPF by regulating the apoptosis of fibroblasts and the senescence of alveolar epithelial cells. In addition, autophagy ameliorates cystic fibrosis lung disease via rescuing transmembrane conductance regulators (CFTRs) to the plasma membrane. Furthermore, autophagy alleviates the silica-induced pulmonary fibrosis by decreasing apoptosis of alveolar epithelial cells in silicosis. However, excessive macrophage autophagy aggravates the pathogenesis of silicosis fibrosis by promoting the proliferation and migration of lung fibroblasts in silicosis. Autophagy is also involved in smoking-induced pulmonary fibrosis, coal workers' pneumoconiosis, ionizing radiation-mediated pulmonary fibrosis and heavy metal nanoparticle-mediated pulmonary fibrosis. In this review, the role and signalling mechanisms of autophagy in the progression of pulmonary fibrosis diseases have been systematically analysed. It has provided a new insight into the therapeutic potential associated with autophagy in pulmonary fibrosis diseases. In conclusion, the targeting of autophagy might prove to be a prospective avenue for the therapeutic intervention of pulmonary fibrosis diseases.

    更新日期:2019-12-23
  • Tumour associated glycans: A route to boost immunotherapy?
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-20
    Emma Scott; David J. Elliott; Jennifer Munkley

    While the development of immunotherapies for cancer treatment offer significant promise across several cancers, still only a small subset of patients respond to immune based monotherapies. As such, attention has turned to the development of combination therapies. These use conventional cancer treatments such as chemotherapy to sensitise tumours to immunotherapy. Here, we summarise key research, highlighting the exciting potential of tumour associated glycans as therapeutic targets to sensitise tumours to immunotherapy. When cells undergo carcinogenesis they reprogram their glyco-code. Several cancer associated glycans have been identified, and therapies targeting them are under development. Proteins containing carbohydrate binding domains (lectins) are expressed by many immune cell subtypes, and upon glycan binding, transduce immune modulatory signals that regulate the tumour immune microenvironment.

    更新日期:2019-12-21
  • Sclerostin within the Chronic Kidney Disease spectrum
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-19
    Antoine Bouquegneau; Peter Evenepoel; François Paquot; Olivier Malaise; Etienne Cavalier; Pierre Delanaye

    Sclerostin is sometimes presented as a promising biomarker in assessing bone health both in the general population and chronic kidney disease patients. However, it is still unclear whether it has any true added value compared to existing bone biomarkers in predicting bone turnover and/or bone density in chronic kidney disease patients. A wealth of papers has been published to evaluate the association between sclerostin and vascular calcifications development or even as prognostic biomarker for mortality, but often with conflicting results. Standardization and harmonization of analytical techniques is a prerequisite to advance clinical knowledge in sclerostin.

    更新日期:2019-12-19
  • Impact of HbA1c variability on subclinical left ventricular remodeling and dysfunction in patients with type 2 diabetes mellitus
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-19
    Suhua Li; Zhenda Zheng; Xixiang Tang; Junlin Zhong; Xing Liu; Yunyue Zhao; Lin Chen; Jieming Zhu; Jinlai Liu; Yanming Chen

    Background  Glycemic instability confers a risk of poor prognosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate whether HbA1c variability provided additional value over mean HbA1c for predicting subclinical left ventricular remodeling and dysfunction in T2DM patients. Methods A total of 466 T2DM patients with normal cardiac structure and function were recruited and prospectively followed up for a median of 4.7 y. HbA1c was measured quarterly. The intrapersonal mean and standard deviation (SD) of HbA1c measurements were calculated, and SD-HbA1c was considered as a measure of HbA1c variability. All participants underwent transthoracic echocardiography at baseline and after follow-up. Results In multivariable regression analyses, SD-HbA1c was independently associated with annualized changes in left ventricular end diastolic diameter, interventricular septum, left ventricular posterior wall, left ventricular mass index, left ventricular ejection fraction, E/e' ratio, and E/A ratio (P <0.001). Subgroup analysis based on mean HbA1c levels (<7.0%, 7.0%∼7.5%, and ≥7.5%) further confirmed that SD-HbA1c was associated with most of the above parameters regardless of mean HbA1c levels. Conclusion This study indicates that HbA1c variability adds to the mean value in predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

    更新日期:2019-12-19
  • Changes of serum interleukin-6 in healthy pregnant women and establishment of relevant reference intervals
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-19
    Yaoyang Fu; Lingli Tang; Min Hu; Qinglin Liu; Zhongyuan Xiang

    Objective To explore the changes of serum interleukin-6 (IL-6) levels in healthy pregnant women and establish reference intervals (RIs). Method According to the requirements for the RIs study model and the reference population screening criteria in C28-A3 document, Serum IL-6 levels were measured by electrochemiluminescence immunoassay in 480 healthy Chinese women, including 120 pregnant women in each of the first, second and third trimester and 120 non-pregnant women as the negative control. The establishment of RIs for IL-6 were defined using nonparametric percentile. Results The RIs for serum IL-6 levels in healthy pregnant women is <4.19pg/ml, the RIs for serum IL-6 levels in healthy pregnant women who are in the first trimester is <3.52pg/ml, and the RIs for serum IL-6 levels in healthy pregnant women who are in the second and third trimester is <4.40pg/ml. Conclusions Serum IL-6 level in healthy pregnant women is higher than the healthy non-pregnant women, and the level of IL-6 who are in the second and third trimester is higher than those in the first. This paper successfully established RIs for serum IL-6 levels in pregnant women, providing a reference for clinical medical staff and laboratory workers.

    更新日期:2019-12-19
  • Tissue kallikrein: a potential serum biomarker to predict delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-19
    Lin Bian; Feng Shen; Lian-Gang Mao; Wei Zhou; Zheng Liu; Guang-Lie Chen

    Background Delayed cerebral ischemia (DCI) is a severe complication after aneurysmal subarachnoid hemorrhage (aSAH). Tissue kallikrein (TK), a subgroup of serine proteinases, is an important component of the kallikrein-kinin system. Exogenous TK attenuated cerebral vasospasm in a rabbit model of subarachnoid hemorrhage. We associated serum TK concentrations with aSAH-related DCI. Methods Serum TK concentrations were detected in a total of 92 aSAH patients and 92 healthy controls. A multivariate logistic regression model was conFig.d to investigate relationship between TK concentrations and occurrence of DCI. Results TK concentrations were substantially lower in aSAH patients than in controls. TK concentrations were strongly correlated with World Federation of Neurological Surgeons (WFNS) score and modified Fisher score. Serum TK, WFNS score and modified Fisher score retained as the three independent predictors for DCI. Under receiver operating characteristic curve, predictive capability of TK concentrations was in the range of WFNS score and modified Fisher score, as well as TK concentrations could remarkably improve predictive abilities of WFNS score and modified Fisher score. Conclusions Serum TK emerges as a potential biomarker for assessment of hemorrhagic severity and prediction of DCI following aSAH.

    更新日期:2019-12-19
  • Mindray SF-Cube technology: an effective way for correcting platelet count in individuals with EDTA dependent pseudo thrombocytopenia
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-18
    Jiankai Deng; Yaoming Chen; Shihong Zhang; Laisheng Li; Qiong Shi; Min Liu; Xuegao Yu

    Several strategies are applied to determine the precise platelet count in individuals with ethylenediaminetetraacetic acid dependent pseudo thrombocytopenia (EDTA-PTCP) caused by in vitro aggregation of platelets in daily laboratory practice. None of them proves optimal for routine purposes. Thus, Mindray has developed the SF-Cube technology coupled with the CDR mode in the Mindray hematology analyzer to overcome the problem of EDTA-PTCP. With Mindray SF-Cube technology, platelet aggregates dissociate effectively and platelets are correctly counted in the CDR mode without pre-analytical management. In our studies, the EDTA-PTCP blood samples when analyzed with the CDR mode of Mindray BC-6800 plus analyzer, yield a markedly higher platelet count compared to those obtained with PLT-I on Sysmex XN-9000 hematology analyzer. We conclude that in patients with known or suspected EDTA-PTCP Mindray SF-Cube technology is a straightforward and effective way of determining the platelet count in EDTA-anticoagulated blood.

    更新日期:2019-12-19
  • Diagnostic performance of 14-3-3η and anti-carbamylated protein antibodies in Rheumatoid Arthritis in Han population of Northern China
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-17
    Yuan Zhang; Yongming Liang; Limei Feng; Liyan Cui

    Objectives As we already know, Rheumatoid arthritis (RA) cannot be excluded when the rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody (anti-CCP) is negative. Here, we determined the application value of 14-3-3η protein, anti-carbamylated proteins antibodies (anti-CarP), as well as their potential role to diagnose RA together with RF or anti-CCP. Method Serum levels of anti-CCP, RF, 14-3-3η and anti-CarP antibodies were detected in 291 RA patients, 223 patients with autoimmune diseases except RA, and 156 healthy subjects recruited from Han population of Northern China. We examined the differences in the levels of these indicators among groups and compared the correlations between any two of the indicators. At the same time, a total of 12 testing strategies were established for comparison to maximize the diagnostic value. Result The levels of RF, anti-CCP, anti-CarP and 14-3-3η were significantly higher in RA patients (12.5;[9.36–15.7], 30.7;[25.7–35.6], 1.90;[1.70–2.01], 15.8;[10.8–20.8], respectively)compared with either interference-control group(1.24;[1.07–1.41], 0.64;[0.42–0.86], 0.51;[0.46–0.57], 0.33;[0.23–0.44], respectively) (p<0.0001) or healthy-control group(1.03;[0.99–1.08], 0.49;[0.38–0.59], 0.28;[0.21–0.35], 0.55;[0.27–0.85], respectively) (p<0.0001). Among all 12 detection strategies, the YI and κ value of a novel strategy that either double-positive of any 2markers or single-positive of anti-CCP can be diagnosed as RA had the highest diagnostic value. Conclusion The results of our study demonstrated that in Han population of Northern China, anti-CarP antibodies and 14-3-3η protein can be treated as valuable indicators of RA, especially when combined with RF and anti-CCP, the detection value is maximized.

    更新日期:2019-12-18
  • Vitamin K role in mineral and bone disorder of chronic kidney disease
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-11
    Rodrigo Bueno de Oliveira, Andréa Emilia Marques Stinghen, Ziad A. Massy

    Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research.

    更新日期:2019-12-11
  • Magnesium: an old player revisited in the context of CKD-MBD
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-11
    M.V. Pendón-Ruiz de Mier, C. Rodelo-Haad, J.M. Díaz-Tocados, J.R. Muñoz-Castañeda, M. Rodríguez

    Chronic kidney disease (CKD) is associated with a wide number of abnormalities in mineral metabolism. Often, these alterations are the leading players in the development of comorbidities associated with CKD, which are risk factors of mortality. In this context, mineral and bone disorder associated with CKD (CKD-MBD) are highlighted, connecting bone, renal, and cardiovascular disorders. Many studies have been led to propose strategies to avoid, reduce, or slow down CKD-MBD progression using different compositions of metallic elements-based P binders such as aluminum, magnesium, or calcium. Magnesium, the aim of this review, has been used by nephrologists to treat CKD-MBD with a variable acceptation due mainly to different results on bone homeostasis. Nowadays, we have new evidence about the efficacy of magnesium supplementation on vascular calcification, renal function, and bone disorders, suggesting potential beneficial effects of Magnesium in the management of CKD-MBD.

    更新日期:2019-12-11
  • Multi-marker Diagnosis Method for Early Hepatocellular Carcinoma Based on Surface Plasmon Resonance
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-11
    Haixia Yu, Ruixue Han, Jie Su, Hailong Chen, Dachao Li

    Early diagnosis of Hepatocellular Carcinoma (HCC) is an important means to raise the survival rate of patients. Multi-marker combined detection is a powerful tool of early HCC diagnosis. Traditional detection methods are not effective and accurate because it is difficult to achieve combined detection of multiple markers. In this paper, we selected Alpha Fetoprotein (AFP) and miRNA-125b as the combined detection markers to improve the simultaneously diagnostic sensitivity and specificity. The anti-AFP monoclonal antibody and the DNA probes paired with the miRNA-125b were modified on the surface of surface plasmon resonance (SPR) sensor respectively to specifically recognize AFP and miRNA-125b in serum. In order to enhance the SPR response signal and detection sensitivity, Double Antibody Sandwich Method (DASM) and S9.6 antibody enhanced method were applied to achieve low detection limit of the two markers. Experimental results showed that AFP (25-400 ng/mL) was accurately detected by DASM and the detection limit of miRNA-125b by S9.6 antibody enhanced method reached 123.044 pM. These results verified the feasibility of the multi-marker detection method in early diagnosis of HCC.

    更新日期:2019-12-11
  • Performance evaluation of 14 specific proteins measurement checked by an External Quality Assessment Scheme
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-10
    Sandra Secchiero, Laura Sciacovelli, Mario Plebani

    Aims of the study: to evaluate the state-of-the-art of 14 specific proteins measurement; to evaluate the laboratories’ performance and the degree of harmonization in reporting results of participants in the External Quality Assessment Program of the Centre of Biomedical Research (CRB). Methods Overall and system-related inter-laboratory analytical variability (mean CVs%) and between-system differences (mean bias%) were evaluated from data of six EQA cycles 2013-2018. Moreover, we evaluated the analytical performance of participants as well as the units used to express proteins results. Results Overall inter-laboratory variability ranged from 3.8% for haptoglobin (HPT) to 12.5 % for α1-antitrypsin (AAT) and decreased for IgA, α2-macroglobulin (A2M) and transferrin (TRF). Mean CVs% were generally higher for Siemens BN and Beckman Immage immunonephelometric systems, but <7.0% for all proteins. Mean bias >7.0% was observed for BN (IgA, C4, AAT, transthyretin TTR), Siemens Vista (IgA, C4) and Immage (C4), whereas mean bias <-7.0% was found for Immage (AAT), Beckman AU (IgM) and Roche Cobas (C4, TTR, C-reactive protein). The laboratories’ performance within the limits ranged from 85.1% of albumin (ALB) to 97.2 % of HPT. The census of units employed in 2018, demonstrated that ∼70% of laboratories still express the results in mg/dL. Conclusions Despite a reduction in inter-laboratory variability for some proteins, different analytical systems showed both proportional and constant bias between methods. Units used by participants have not been substantially changed and dL is still largely used. The CRB EQA Program, with its performance data sets, is a valuable resource for laboratories and IVD manufacturers and support the goals of harmonization.

    更新日期:2019-12-11
  • Clinical significance of urinary plasminogen and fibrinogen gamma chain as novel potential diagnostic markers for non-small-cell lung cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-09
    Wencheng Zhang, Zhouyong Gao, Guang Zeng, Hui Xie, Jinbo Liu, Ning Liu, Guangshun Wang

    Background Urinary proteins could be useful as markers for the detection of non-small-cell lung cancer (NSCLC). We investigated the levels of two different proteins in urine samples from NSCLC patients and assessed their diagnostic value. Methods Urinary plasminogen (PLG) and fibrinogen gamma chain (FGG) levels in 112 NSCLC patients and 197 controls were detected using enzyme linked immunosorbent assay (ELISA). The expression of FGG and PLG in 20 NSCLC tissues and paired adjacent non-tumour tissues were detected through immunohistochemistry. The diagnostic value of FGG and PLG for NSCLC was evaluated through a receiver operating characteristic curve (ROC). Results PLG and FGG were significantly elevated in NSCLC tissues vs paired adjacent non-tumour tissues (p=0.000) and in urinary samples from NSCLC patients vs healthy controls (p=0.000). The expression level of PLG in urinary samples was related only to the histological type (p=0.001). Further, ROC curve analysis revealed that PLG, FGG, and their combination could distinguish NSCLC and its subtypes from healthy controls with an AUC ranging from 0.827 to 0. 947. By comparing urine samples with matching plasma CEA from NSCLC stage I-IV patients (n=81) and healthy controls (n=31), the combination of CEA with PLG or FGG showed that the AUC was 0.889 and 0.806, respectively, which is superior to a single biomarker alone. Conclusions These two urinary proteins could serve as potential markers for the diagnosis of NSCLC.

    更新日期:2019-12-09
  • The association between C-reactive protein and common blood tests in apparently healthy individuals undergoing a routine health examination
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-06
    Tomer Ziv-Baran, Asaf Wasserman, Ilana Goldiner, Moshe Stark, Shani Shenhar-Tsarfaty, Itzhak Shapira, David Zeltser, Inna Mailis, Shlomo Berliner, Ori Rogowski

    Background C-reactive protein (CRP) is considered a marker of inflammation. We sought to evaluate the association between CRP level and commonly use blood tests in apparently healthy population. Methods A cross-sectional study of all visits in a routine health examination center between 1/2002 and 7/2018. CRP, complete blood count and chemistry blood panel were evaluated in each visit. Visits of individuals who had CRP above the 99th percentile or use statins were excluded. Correlation between CRP and blood tests was evaluated in the whole cohort as well as in sub-populations. Results Blood parameters of 33,261 visits were included. Moderate positive correlation between CRP and white blood cells count (r=0.269), neutrophils count (r=0.275), triglycerides (r=0.275), alkaline phosphatase (r=0.221) and gamma glutamyl transpeptidase (r=0.220) was evaluated. Correlation with triglycerides was stronger in female then in males (r=0.38 vs. 0.25). Uric acid was positively correlated in females and males. In participants under 30 years, inverse correlation with hemoglobin, creatinine and albumin levels and positive correlation with cholesterol were documented. Conclusion Significant moderate association between CRP and several blood tests was evaluated in apparently healthy population. This information should be used for further studies of the relationship between inflammation and biological processes.

    更新日期:2019-12-07
  • Plausibility of an extensive use of stool DNA test for screening advanced colorectal neoplasia
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-06
    Jiayi Mu, Yanqin Huang, Shanrong Cai, Qilong Li, Yongmao Song, Ying Yuan, Suzhan Zhang, Shu Zheng

    Purpose FIT-DNA test is supposed to be highly sensitive for advanced colorectal neoplasms and is advocated in some developed countries, but lack extensive use in developing countries. Methods A case control study on stool DNA test for colorectal neoplasms patients was conducted from March 2016 to October 2017 in China. We recruited CRC, colorectal neoplasms and normal controls from ambulatory patients and screening attendees in communities. The stool DNA was tested by a molecular panel similar as ColoGuard in addition to fecal immunochemical test(FIT) in a blinded manner. A risk scoring system was used to determine the positiveness of tests with histological diagnosis as its reference standard. Results Eligible subjects included 203 colorectal cancer (CRC), 49 advanced adenoma (AA), 156 non-advanced adenoma(NAA) and 431 normal controls(NC). The FIT-DNA kit detected 97.5% CRC (n=198, 95% CI=95.4-99.7) and 53.1% AA (n=26, 95% CI=39.1-67.0), with specificity of 89.1% (95%CI=86.2-92.0) in NC and 88.1% (95%CI=85.5-90.7) in non-advanced controls. The FIT embedded in the kit alone identified 94.6% (n=192, 95% CI=91.5-97.7) CRC and 36.7% AA (n=18, 95% CI=23.2-50.2). Consistency of KRAS mutation, BMP3 methylation, NDRG4 methylation in 26 paires stool DNA and CRC tumor DNA were 80.9%, 71.4% and 81.8%, respectively Conclusion At the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.

    更新日期:2019-12-07
  • MicroRNA and Retinoic Acid
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-05
    Reza Gholikhani-Darbroud

    Background and objective Retinoic acid is a metabolite of vitamin A that is necessary to maintain health in human and most of the other vertebrates. MicroRNAs (miR or miRNAs) are small, non-coding RNA particles that diminish mRNA translation of various genes and so can regulate critical cell processes including cell death, proliferation, development, etc. The aim of this review is to study interrelations between retinoic acid with miRNAs. Methods We reviewed and summarized all published articles in PubMed, Europe PMC, and Embase databases with any relationship between retinoic acid and miRNAs from Jun 2003 to Dec 2018 that includes 126 articles. Results Results showed direct and indirect relationships between retinoic acid and miRNAs in various levels including effects of retinoic acid on expression of various miRNAs and miRNA-biogenesis enzymes, and effect of miRNAs on metabolism of retinoic acid. Discution and conclusion This review indicates that retinoic acid has inter-correlations with various miRNA members and their metabolism in health and disease may require implications of the other.

    更新日期:2019-12-05
  • Antenatal Maternal Antidepressants Drugs Treatment Affects S100B Levels in Maternal-Fetal Biological Fluids in a Dose Dependent Manner
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-04
    Valentina Bellissima, Gerard HAVisser, Tessa Ververs, Francesca Pluchinotta, Alessandro Varrica, Ekaterina Baryshnikova, Lucia Gabriella Tina, Francesco Nigro, Danilo Gavilanes, Justyna Godos, Diego Gazzolo

    Background The increased use of antidepressant treatment during pregnancy occurred without firm evidence on safety/efficacy. The present study investigated the correlation among S100B and paroxetine blood levels with the occurrence of short-term post-natal neurological abnormalities. Methods We conducted a cross-sectional study in 50 pregnant women using paroxetine because of depression and in 150 controls. Standard laboratory parameters and S100B were measured at seven monitoring time-points (maternal blood: T1, 16-20 wks; T2, 27-30 wks; T3, 35-40 wks; T4, at delivery; amniotic fluid,T5; venous and arterial cord blood, T6-T7). Paroxetine levels were measured at T1-T6. Neurological outcome was set at 7th day from birth. Results Higher S100B concentrations at T1-T7 were found in the paroxetine-treated group. S100B correlated with paroxetine blood levels. The paroxetine/S100B ratio cut-off of 1.31 at T2 achieved sensitivity 100%, specificity 96.5% and positive/negative predictive values 87.5-100, respectively, as a single marker to predict adverse neonatal neurological outcome. Conclusions the present study offers additional support to the usefulness of longitudinal S100B and drug level monitoring in depressed pregnant women and in the early detection of cases at risk for short-term neurological abnormalities. Results open the way at further investigations correlating antidepressant drugs and neurobiomarkers in the maternal bloodstream.

    更新日期:2019-12-04
  • Diagnostic value of hematological parameters platelet to lymphocyte ratio and hemoglobin to platelet ratio in patients with colon cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-03
    Zuojian Hu, Shaolin Tan, Siyuan Chen, Shanzi Qin, Huaping Chen, Simeng Qin, Zhili Huang, Fengyuan Zhou, Xue Qin

    Objective This study was designed to retrospectively analyze the value of the hematological parameter platelet to lymphocyte ratio (PLR) and hemoglobin to platelet ratio (HPR) in patients with colon cancer. Methods The hematological parameters and clinical data of 354 cases patients with colon cancer, 108 cases patients with benign colon tumors and 123 healthy controls were collected from our hospital electronic medical records. Results Compared with the colon benign tumor group and the healthy control group, the colon cancer group had an increased PLR value and a decreased HPR value. The correlation between the clinicopathological features and the laboratory parameters of colon cancer patients was analyzed, and the results showed that both PLR and HPR were associated with tumor invasion and tumor size. Compared with PLR (AUC=0.725, 95%CI: 0.682 - 0.765), HPR (AUC=0.752, 95%CI: 0.710 - 0.790) or carcinoembryonic antigen (CEA) (AUC=0.710, 95%CI: 0.666 - 0.751) used alone, the combination with PLR and CEA (AUC=0.790, 95%CI: 0.750 - 0.826) or with HPR and CEA (AUC=0.814, 95%CI: 0.775 - 0.848) can improve specificity and produce greater AUC in differentiating colon cancer from benign colon cancer. Conclusion Combined application of PLR, HPR, and CEA may improve the diagnostic efficacy of distinguishing between colon cancer and benign colon tumors.

    更新日期:2019-12-04
  • Interaction of lipoprotein(a) with low-density lipoprotein cholesterol on first incident acute myocardial infarction
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-03
    Yong Hu, Jian-Ying Tao, Dong-Ping Cai, Yong-Ming He

    Objective To evaluate the interaction effects between lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) on first incident acute myocardial infarction (AMI) among Chinese Han population. Methods 1522 cases and 1691 controls were retrospectively analyzed. All subjects were grouped by Lp(a) or LDL-C level. Results Compared with reference group (LDL-C<2.6mmol/L and in the 1st quintile of Lp(a)), multivariable-adjusted analysis revealed that OR(95%CI) of first incident AMI for higher LDL-C alone is 2.66(1.78-3.98); that ORs(95%CI) for higher Lp(a) alone are 1.51(1.07-2.15), 1.84(1.28-2.64), 1.86(1.30-2.67) and 2.66(1.88-3.76) across the Lp(a) quintiles; and that ORs(95%CI) for both higher LDL-C and higher Lp(a) are 3.95(2.64-5.92), 3.20(2.21-4.64), 5.64(3.80-8.36) and 7.48(4.90-11.44) which were greater than the sum of the risks of both alone across the Lp(a) quintiles. Relative excess risks due to interaction were 1.78(95% CI, 0.12-3.44, P=0.036) and 3.01(0.58-5.44, P=0.015) at the 4th and 5th quintile of Lp(a), confirming the presence of additive interaction between Lp(a) and LDL-C on initial AMI. Conclusions Lp(a) interacts with LDL-C in first incident AMI on additive scale in Chinese Han population. The risk of initial AMI from exposure of elevated Lp(a) combined with elevated LDL-C is much greater than the sum of the risks from that of both alone.

    更新日期:2019-12-04
  • Diagnostic test accuracy of droplet digital PCR for the detection of EGFR mutation (T790M) in plasma: systematic review and meta-analysis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-02
    Yingyin Liao, Yuan Chen, Xiaoxia Kou, Yi Xiao, Junkai Ye, Aiwu Wu

    Background T790M mutation was a primary lead cause in the acquired resistance to EGFR-TKIs confirmed in earlier studies. Since the shortcomings of tumor tissue detection are well known, the liquid biopsy is more appropriate to track T790M status. We assessed the accuracy and clinical significance of the droplet digital PCR (ddPCR) detection of T790M mutation in plasma. Methods We retrieved PubMed, Embase, Cochrane, and Web of science with no limitation of language and publication year. Summary sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio of detection of EGFR T790M status were calculated from extracted data from included articles. The summary receiver operating curve (SROC), diagnostic odds ratio (DOR), and the area under the summary receiver operating curve (AUC) was used to assess the overall diagnostic accuracy. I2 and meta-regression were used to evaluate heterogeneity and the source of heterogeneity, respectively. Result We identified 15 studies in the total search of 1364 reports, including 427 paired tissue and plasma samples. The pooled sensitivity and the pooled specificity were 0.68 (95% CI 0.61-0.75) and 0.85 (95% CI 0.75-0.91) by the bivariate model, respectively. The AUC and the pooled DOR were 0.78 (95% CI 0.74-0.81) and 12 (95% CI 7-22), respectively. None of the cofactors could account for the heterogeneity. Conclusion The plasma analysis is of a promising performance to screen EGFR-T790M mutation status by ddPCR.

    更新日期:2019-12-02
  • An overlap of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and IgG4-related kidney disease
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-12-02
    Zhi-Ying Li, Xu Wang, Xi Xia, Xiao-Juan Yu, Su-Xia Wang, Wei Chen, Min Chen, Ming-Hui Zhao

    Background We investigated the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) and immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD) overlap syndrome. Methods Thi is a 2-center study with 19 patients. Results Fifteen patients were classified as microscopic polyangiitis (MPA). The initial serum creatinine levels were 320.9±191.4 μmol/l and the BVAS was 19.7±7.4 at diagnosis. Hematuria was absent or slight in 13 (68.4%) cases. Renal histology of these patients revealed concurrent ANCA-GN and IgG4-RKD. Regarding the histological classification of ANCA-GN, 9 (47.4%), 8 (42.1%), 1 (5.3%) and 1 (5.3%) patients were classified as focal, crescentic, mixed and sclerotic ANCA-GN, respectively. MPO-ANCA could be detected in 17/19 (89.5%) patients. IgG subclasses of MPO-ANCA were tested in 10 patients, and all were positive for IgG4-MPO-ANCA. In patients with combined ANCA-GN and IgG4-RKD, the percentage of positive IgG1-MPO-ANCA was significantly lower than the control group of 20 AAV patients without IgG4-RKD (P=0.002), and the percentage of positive IgG4-MPO-ANCA was higher than the control group, but this difference was not statistically significant (P=0.14). Conclusions ANCA-GN and IgG4-RKD overlap syndrome concerned mainly MPO-ANCA positive patients. The IgG subclass analysis of MPO-ANCA showed lower percentage of IgG1 subclass. The association between ANCA-GN and IgG4-RKD is possible and represents a special entity.

    更新日期:2019-12-02
  • One Potential Hotspot ACADVL Mutation in Chinese Patients with Very-long-chain Acyl-coenzyme A Dehydrogenase Deficiency
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    Xiyuan Li, Rui Ma, Yi Liu, Lulu Kang, Ruxuan He, Jinqing Song, Jing Ren, Yang Li, Min Huang, Jianlong Men, Yanling Yang

    Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD deficiency), a rare autosomal recessive disorder, is characterized by hypoketotic hypoglycemia, cardiomyopathy, liver damage, and myopathy. VLCAD deficiency is caused by defects of ACADVL gene, which encodes VLCAD protein. The aim of this study was to determine the clinical, biochemical, prognosis and mutation spectrum of patients with VLCAD deficiency in mainland China. A total of Six families visited us, four patients (2 boys and 2 girls) were admitted in hospital due to liver dysfunction, hypoglycemia, and positive newborn screen result. The parents of the other two patients (2 girls) visited us for genetic consultation after their children's death. All the six patients had elevated level of serum tetradecenoylcarnitine (C14:1-carnitine), four of them showed decreased free carnitine (C0) level, and three had dicarboxylic aciduria. Eight types of mutations of the ACADVL gene were detected, three of them are novel, including c.563G>A (p.G188D) c.1387G>A (p.G463R) and c.1582_1586del (p.L529Sfs*31). The p.R450H mutation accounts for 9/52 alleles (5/40 in previous study of 20 unrelated patients, and 4/12 in this study) of genetically diagnosed Chinese VLCAD deficiency cases. The four alive patients (Patient 1-4) responded well to diet prevention and drug therapy with stable hepatic dysfunction condition. In conclusion, we describe three novel mutations of the ACADVL gene among six unrelated families with VLCAD deficiency. Moreover, we suggest that the p.R450H may be a potential hotspot mutation in the Chinese population.

    更新日期:2019-11-30
  • Validation and evaluation of four sample preparation methods for the quantification of intracellular tacrolimus in peripheral blood mononuclear cells by UHPLC-MS/MS
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    Lisanne N. van Merendonk, Pere Fontova, Raül Rigo-Bonnin, Helena Colom, Anna Vidal-Alabró, Oriol Bestard, Juan Torras, Josep M. Cruzado, Josep M. Grinyó, Núria Lloberas
    更新日期:2019-11-30
  • Functional immune assay using interferon-gamma could predict infectious events in end-stage kidney disease
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    S. Boyer-Suavet, M. Cremoni, T. Dupeyrat, K. Zorzi, V. Brglez, S. Benzaken, V. Esnault, B. Seitz-Polski

    Background Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events. Methods In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-γ) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months. Results QuantiFERON-Monitor showed lower stimulated IFN-γ production in ESKD patients (n=54) compared to healthy donors (n=19) (p<0.0001) and to chronic kidney disease stage 3-4 patients (n=7) (hemodialysis (n=30): p<0.01; peritoneal dialysis (n=13): p=0.03 and ESKD on conservative management (n=11): p<0.001). No significant difference in stimulated IFN-γ production was observed between ESKD patients with renal replacement therapies or conservative management. Stimulated IFN-γ production was significantly lower in patients later developing infections (13.9 [5.5-48.3] IU/mL vs 85.8 [35.5-236] IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity =79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-γ levels measured by QuantiFERON Monitor below 63.55 IU/mL (n=21) had a hazard ratio of 10.71 ([3.68-31.13], p < 0.0001) for the development of subsequent infections. Conclusion Monitoring of IFN-γ production after stimulation of innate and adaptive immunity may identify ESKD patients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.

    更新日期:2019-11-30
  • Monocyte lymphocyte ratio predicts the new-onset of chronic kidney disease: a cohort study
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    Meng Zhang, Kun Wang, Huabo Zheng, Xiaofang Zhao, Songpu Xie, Chengyun Liu

    Background and Aims The role of monocyte lymphocyte ratio (MLR) in predicting the risk of chronic kidney disease (CKD) is unclear, although inflammation contributes to the development of CKD. This study aimed to investigate whether elevated MLR predicts new-onset CKD. Methods This study enrolled 14033 consecutively Chinese participants. The primary outcome was the new-onset CKD defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 or the presence of proteinuria after follow-up. After the descriptive analyses of baseline data, Univariate and multivariate Cox proportional models were used to evaluate the independent relationship between MLR and new-onset CKD. Results 11280 participants were included in the final analysis, and 58.44%(n=6592) of them were male. The mean age was 44.67 ± 12.85 years. After a median follow-up of 1.94 years, 2.55% (n=288) of participants developed new-onset CKD. MLR was associated with the increased risk of CKD (HR=16.12, 95% CI=4.52-57.56, p<0.0001). After adjustment for age, gender, body mass index, history of hypertension, systolic blood pressure, high-density lipoprotein cholesterol, triglyceride, fasting plasma glucose, uric acid and estimated glomerular filtration rate, MLR remained an independent risk factor for CKD (HR=8.89, 95%CI=2.18-36.27, p=0.0023). Conclusion MLR is an independent predictor of the risk of CKD, which might be expected to better guide early prevention and treatment interventions.

    更新日期:2019-11-30
  • S100 Proteins in Atherosclerosis
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    Xuan Xiao, Chen Yang, Shun-Lin Qu, Yi-Duo Shao, Chu-Yi Zhou, Ru Chao, Liang Huang, Chi Zhang

    Atherosclerosis is an arterial disease associated with dyslipidemia, abnormal arterial calcification and oxidative stress. It has been shown that a continued chronic inflammatory state of the arterial wall contributes to the development of atherosclerosis. The inflammatory stimulation, recruitment of inflammatory cells and production of pro-inflammatory cytokines enhances vascular inflammation. Some members of the S100 proteins family bind with their receptors, such as advanced glycation end products (RAGE), scavenger receptors (CD36) and toll-like receptor 4 (TLR-4), contributing to the cellular response in atherosclerotic progression. This review summarizes the roles of S100 proteins (S100A8, S100A9 and S100A12) in the vascular inflammation, vascular calcification and vascular oxidative stress. S100 proteins are released from monocytes, smooth muscle cells and endothelial cells in response to cellular stress stimuli, and then the binding of S100 proteins to RAGE activate downstream signaling such as transcription factor kappa B (NF-κB) translocation and reactive oxygen species (ROS) production, which act as a positive feedback loop for inducing pro-inflammatory phenotype in a wide variety of cell types including endothelial cells, vascular smooth muscle cells and leukocytes. Thus, it suggests that the inhibition of S100 proteins-mediated RAGE and TLR4 activation appears to be a promising approach to treat atherosclerosis. In addition, recent study showed that serum S100A12 can predict future cardiovascular events, highlighting that S100A12 is likely to be a potential biomarker of therapeutic efficacy and disease progression in coronary heart disease. Future studies of patients with coronary heart disease may provide more evidences supporting that S100 proteins is promising drug target in the prevention and therapy of atherosclerosis.

    更新日期:2019-11-30
  • Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer
    Clin. Chim. Acta (IF 2.735) Pub Date : 2019-11-30
    Zhaolei Cui, Yansong Chen, Minhua Hu, Yingfeng Lin, Shuyu Zhang, Lingying Kong, Yan Chen

    Background Lactate dehydrogenase C4 (LDH-C4) as a cancer/testis antigen (CTA) is abnormally expressed in some malignant tumors. However, the expression and clinical significance of LDH-C4 in breast cancer (BC) has not been characterized. Methods We determined LDHC mRNA expression in serum and serum-derived exosomes of BC patients by quantitative RT-PCR. We also evaluated the protein expression of LDH-C4 in BC tissues using high-throughput tissue microarray analysis and immunohistochemistry. Results Our results showed high mRNA expression level of LDHC in serum and serum-derived exosomes of BC patients. The LDHC level in serum and exosomes could distinguish BC cases from healthy individuals based on their AUCs of 0.9587 and 0.9464, respectively. Besides, the LDHC level in exosomes of BC patients associated with tumor size, and positively correlated with HER2 and Ki-67 expressions (all with P < 0.05). Serum and exosomal level of LDHC negatively correlated with medical treatment and positively with the recurrence of BC. Survival analysis showed that LDH-C4 expression negatively correlated with BC prognosis. Conclusion Serum and exosomal LDHC may be an effective indicator for the diagnosis, efficacy evaluation, and monitoring the recurrence of BC. LDH-C4 may act as a biomarker that predicts BC prognosis.

    更新日期:2019-11-30
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