Yongzhe Li

Construction of A Multiple Myeloma Diagnostic Model by Magnetic Bead-Based MALDI-TOF Mass Spectrometry of Serum and Pattern Recognition Software

A diagnosis of multiple myeloma (MM) is difficult to make on the basis of any single laboratory test result. Accurate diagnosis of MM generally results from a number of costly and invasive laboratory tests and medical procedures. The aim of this work is to find a new, highly specific and sensitive method for MM diagnosis. Serum samples were tested in groups representing MM (n = 54) and non‐MM (n = 108). These included a subgroup of 17 plasma cell dyscrasias, a subgroup of 17 reactive plasmacytosis, 5 B cell lymphomas, and 7 other tumors with osseus metastasis, as well as 62 healthy donors as controls. Bioinformatic calculations associated with MM were performed. The decision algorithm, with a panel of three biomarkers, correctly identified 24 of 24 (100%) MM samples and 46 of 49 (93.88%) non‐MM samples in the training set. During the masked test for the discriminatory model, 26 of 30 MM patients (sensitivity, 86.67%) were precisely recognized, and all 34 normal donors were successfully classified; patients with reactive plasmacytosis were also correctly classified into the non‐MM group, and 11 of the other patients were incorrectly classified as MM. The results suggested that proteomic fingerprint technology combining magnetic beads with MALDI‐TOF‐MS has the potential for identifying individuals with MM. The biomarker classification model was suitable for preliminary assessment of MM and could potentially serve as a useful tool for MM diagnosis and differentiation diagnosis. Anat Rec, 292:604–610, 2009.

Promising diagnostic biomarkers for primary biliary cirrhosis identified with magnetic beads and MALDI-TOF-MS.

(PBC) is not a rare disease worldwide. Most patients are diagnosed at the advanced stage, primarily because there are not yet any valid biomarkers available for early diagnosis. Useful biomarkers are absolutely necessary for early detection of PBC. Fortunately, the use of MALDI‐TOF‐MS and pattern recognition software has been successful in finding specific markers for the early detection of the disease. To screen for potential protein biomarkers in the serum for diagnosing PBC, MALDI‐TOF‐MS combined with magnetic beads and pattern recognition software was used to investigate 119 serum samples from 44 patients with PBC, 32 controls with other hepatic disease, and 43 healthy controls. A total of 69 discriminant m/z peaks were identified as being associated with PBC. Of them, the m/z peaks at 3445, 4260, 8133, and 16,290 were used to construct a model for the diagnosis of PBC. This diagnostic model can distinguish PBC from non‐PBC controls with a sensitivity of 93.3% and a specificity of 95.1%. In our blind test, it demonstrated good sensitivity and specificity: 92.9% and 82.4%, respectively. These results indicate that useful serum biomarkers for PBC can be discovered by MALDI‐TOF‐MS combined with the use of magnetic beads and pattern recognition software. The pattern of multiple markers provides a powerful and reliable diagnostic method for PBC with high sensitivity and specificity. Anat Rec, 292:455–460, 2009.

Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Arthritis

Objective The anti-carbamylated protein (CarP) antibody is a novel biomarker that might help in the diagnosis of rheumatoid arthritis (RA). We aim to assess the diagnostic value of anti-CarP antibody for RA. Methods We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for studies published by December 15, 2015. Studies in any language that evaluated the utility of the anti-CarP antibody in the diagnosis of RA in which healthy donors or patients without arthritis or arthralgia served as controls were included. Two investigators independently evaluated studies for inclusion, assessed study quality and abstracted data. A bivariate mixed-effects model was used to summarize the diagnostic indexes from 7 eligible studies. Results The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CarP antibody were 42% (95% CI, 38% to 45%), 96% (95% CI, 95% to 97%), 10.2 (95% CI, 7.5 to 13.9), and 0.61 (95% CI, 0.57 to 0.65), respectively. The summary diagnostic odds ratio was 17 (95% CI, 12 to 24), and the area under summary receiver operator characteristic curve was 80% (95% CI, 77% to 84%). Conclusion Anti-CarP antibody has a moderate value in the diagnosis of RA with high specificity but relatively low sensitivity.

Biomarkers for the Prediction of Major Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome

The aim of this study is to find novel biomarkers for prognosis in patients with acute coronary syndrome (ACS). We enrolled 245 eligible patients with ACS and compared the protein expression between the two groups, with or without major adverse cardiovascular events (MACE). To determine biomarkers for prognosis, we performed mass spectrometry analysis. We found 10 proteins in the serum that can be used to classify ACS with or without MACE and specific protein peaks at m/z 1921.0, 2124.2, and 20887.3 that were increased in patients with MACE. These peaks reliably predict MACE occurrence in patients with ACS, in addition to the widely accepted markers troponin and brain natriuretic peptide precursor. The characteristic changes in the peaks at m/z 1921.09, 2124.2, and 20887.3 correlate with poor prognosis in ACS patients. These proteins could potentially be used as predictive biomarkers to evaluate patient prognosis. Anat Rec 293:1512–1518, 2010.

Establishing a reference interval for serum anti-dsDNA antibody: A large Chinese Han population-based multi-center study

Background A reference interval (RI) for the circulating concentration of anti-dsDNA antibody is essential for clinicians to interpret laboratory results and make clinical decisions. Therefore, we aimed to establish the RI for anti-dsDNA antibody in the Chinese Han population. Methods This study was designed and carried out in accordance with guideline C28-A3, which is proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. A total of 2,880 apparently healthy individuals were enrolled using a posteriori sampling. These individuals were recruited from four hospitals, representing the Han populations of north, south, east, and west China. Serum anti-dsDNA antibody levels were measured using the three analytical systems AESKU, EUROIMMUNE, and INOVA, which are the most commonly used systems in China. Individuals were stratified by gender, age, and region, and the RIs were obtained by nonparametric methods. Results Gender-specific RIs for serum anti-dsDNA antibody in the Chinese Han population were established. Conclusion This is the first exploration of the RI for anti-dsDNA antibody in the Chinese Han population. We have established gender-specific RIs for each assay method commonly used in China.

A reference interval for serum IgG subclasses in Chinese children

Background Reference intervals (RIs) for serum IgG subclasses vary greatly among different geographical regions. The present study aimed to establish RIs for serum IgG subclasses in Chinese children, which is essential for interpretation of laboratory findings and making clinical decisions. Methods This study was performed in accordance with guideline C28-A3, proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. In total, 607 apparently healthy Chinese children were enrolled, and serum levels of IgG subclasses were measured. Individuals were stratified by age and the RIs were determined through statistical analysis. Results Following were the median values of RIs for serum IgG subclasses in Chinese children: IgG1, 2.78 g/L; IgG2, 0.85 g/L; IgG3, 0.13 g/L; IgG4, 0.06 g/L at 1–6 months of age; IgG1, 3.64 g/L; IgG2, 0.73 g/L; IgG3, 0.19 g/L; IgG4, 0.03 g/L at 6–12 months of age; IgG1, 5.15 g/L; IgG2, 0.87 g/L; IgG3, 0.19 g/L; IgG4, 0.07 g/L at 1–2 years of age; IgG1, 5.26 g/L; IgG2, 1.23 g/L; IgG3, 0.14 g/L; IgG4, 0.11 g/L at 2–3 years of age; IgG1, 6.33 g/L; IgG2, 1.8 g/L; IgG3, 0.2 g/L; IgG4, 0.21 g/L at age 3–4 years; IgG1, 7.05 g/L; IgG2, 1.87 g/L; IgG3, 0.25 g/L; IgG4, 0.29 g/L at 4–6 years of age; IgG1, 6.19 g/L; IgG2, 1.93 g/L; IgG3, 0.2 g/L; IgG4, 0.28 g/L at 6–9 years of age; IgG1, 6.76 g/L; IgG2, 2.29 g/L; IgG3, 0.27 g/L; IgG4, 0.37 g/L at 10–12 years of age; IgG1, 7.45 g/L; IgG2, 2.92 g/L; IgG3, 0.28 g/L; IgG4, 0.38 g/L at 13–16 years of age. Conclusion To our knowledge, this study is the first to establish RIs for serum IgG subclasses exclusively in Chinese children.

NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the Chinese population: A case-control study

The incidence of dilated cardiomyopathy (DCM) has increased in recent years, and many studies have sought to further improve the general understanding of this condition. Previous studies have demonstrated that some single nucleotide polymorphisms (SNPs) associated with systemic lupus erythematosus also affect susceptibility to DCM, suggesting that immune‐related diseases may share similar genetic susceptibility. Recent large‐scale and genome‐wide association studies have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as genetic risk factors associated with cardiac manifestations of neonatal lupus. Here, we aimed to determine whether these SNPs conferred susceptibility to DCM in the Chinese Han population.

Single-nucleotide rs738409 polymorphisms in the PNPLA3 gene are strongly associated with alcoholic liver disease in Han Chinese males

ObjectiveAlcoholic liver disease (ALD) is a chronic liver disorder caused by the consumption of large amounts of alcohol. Genome-wide association studies have recently confirmed that polymorphisms in PNPLA3 predispose individuals to ALD and have identified risk loci of MBOAT7 and TM6SF2 in persons of European descent. However, the association with alcoholic liver damage has not been evaluated thus far in a Han Chinese population.MethodsWe performed a large case-control multicenter study of 507 ALD patients and 645 ethnically matched healthy controls. Five SNPs were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry, and association analysis was performed using PLINK 1.07 software.ResultsThe rs738409 in the PNPLA3 gene was found to be significantly associated with ALD in allele and genotype frequencies (pu2009=u20096.25u2009×u200910−14 and pu2009=u20099.05u2009×u200910−13). The frequencies of the risk allele G in rs738409 were notably higher in ALD compared to controls (odds ratiou2009=u20091.93, 95% confidence intervalu2009=u20091.63–2.28). The current study showed that the genotype frequencies of three genetic models were also statistically significant (pu2009=u20091.07u2009×u200910−13, pu2009=u20099.3u2009×u200910−8, and pu2009=u20091.57u2009×u200910−12). Additionally, the G-allele of rs738409 was associated with a variety of clinical manifestations such as elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV) in the patients with ALD.ConclusionIn a Han Chinese population, the present study confirmed that PNPLA3 polymorphism rs738409 was more likely to influence the susceptibility to ALD. However, no statistically significant differences for the allele and genotype frequencies of rs626283, rs641738 in MBOAT7, rs10401969 in SUGP1 and rs58542926 in TM6SF2 were found between ALD patients and healthy controls.

NCOA1 is a novel susceptibility gene for multiple myeloma in the Chinese population: A case-control study.

Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population. In 827 MM cases and 709 healthy controls of Chinese Han, seven single nucleotide polymorphisms (SNPs) in the HLA–I region (rs6457327), the HLA–II region (rs2647012 and rs7755224), the CXCR5 gene (rs4938573), the ETS1 gene (rs4937362), the LPP gene (rs6444305), and the NCOA1 region (rs79480871) were genotyped using the Sequenom platform. Our study indicated that genotype and allele frequencies of rs79480871 showed strong associations with MM patients (pa = 3.5×10−4 and pa = 1.5×10−4), and the rs6457327 genotype was more readily associated with MM patients than with controls (pa = 4.9×10−3). This study was the first to reveal the correlation between NCOA1 gene polymorphisms and MM patients, indicating that NCOA1 might be a novel susceptibility gene for MM patients in the Chinese Han population.