Association of serum vitamin D status with gestational diabetes mellitus and other laboratory parameters in early pregnant women.

BACKGROUND: The association between serum 25-hydroxy vitamin D (25(OH)D) status and gestational diabetes mellitus (GDM) gained attention in recent years, however the conclusion is still controversial due to many interfering factors, such as region of living, environment, lifestyle, and food supplements. Other metabolites (laboratory parameters) are also important in reflecting gestational states. This study aimed to investigate the association of serum 25(OH)D status in early pregnancy with GDM and other laboratory parameters in pregnant women. METHODS: A total of 1516 pregnant women whose blood glucose were normal before pregnancy in the city of Foshan in Guangdong, China were enrolled in this study. GDM was diagnosed between 24 to 28 weeks of pregnancy following the guidelines from the American Diabetes Association. Maternal serum 25(OH)D and other laboratory parameters-including hematology, coagulation, chemistry, and bone density-were measured utilizing various analytical methods in clinical laboratory at gestational weeks 11 to 14. RESULTS: The average 25(OH)D concentration was 59.1 ± 12.6 nmol/L. None of the study subjects had 25(OH)D < 25 nmol/L; 434 (28.6%) women had 25(OH)D deficiency (< 50 nmol/L), 882 women (58.2%) had 25(OH)D insufficiency (50-74 mmol/L) and 200 women (13.2%) had 25(OH)D sufficiency (≥ 75 nmol/L). There were 264 (17.4%) women diagnosed with GDM. There was not, however, an association between serum 25(OH)D in early pregnancy and GDM. Interestingly, women with more parity and high serum alkaline phosphatase levels had higher serum 25(OH)D levels. There was a possible positive association between serum 25(OH)D and pre-albumin, and a possible negative association between serum 25(OH)D, creatinine, and thrombin time. This study did not find an association between serum 25(OH)D and bone density. CONCLUSIONS: There were no associations between maternal serum 25(OH)D concentration in early pregnancy and the risk of GDM or bone density. There were, however, correlations between serum 25(OH)D and parity, seasoning at sampling, serum alkaline phosphatase, creatinine, pre-albumin, and coagulation factor thrombin time, which need further study to explain their pathophysiology and clinical significance.

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China.

BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. METHODS: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. RESULTS: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). CONCLUSIONS: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.

A Misdiagnosed Atypical Case of Diffuse Large B Cell Lymphoma Diagnosed by Computed Tomography Guided Spleen Biopsy.

BACKGROUND: Lymphoma is a malignancy of hematopoietic and lymphoid tissues. Early diagnosis of lymphoma is very important and could save patients' lives. Nevertheless, the diagnosis of lymphoma could be difficult in the presence of complex manifestations and a lack of convincing laboratory findings. Here we report a case of large B cell lymphoma misdiagnosed as hemophagocytic syndrome during the hospitalization and treatment course. METHODS AND RESULTS: Retrospective review of patient's clinical data, differential diagnosis, and treatment were performed. Patient's disease course was followed and the final diagnosis, along with relevant discussions and summaries were documented. CONCLUSIONS: This report may be helpful in the diagnosis of lymphoma with complex manifestations differentiated from hemophagocytic syndrome, and may facilitate early diagnosis and treatment.

Correlations of disease severity and age with hematology parameter variations in patients with COVID-19 pre- and post-treatment.

BACKGROUND: For better understanding of the pathological changes of COVID-19, benefiting clinical management of the disease and the preparation for future waves of similar pandemics. METHODS: Hematology parameters from a total of 52 cases of COVID-19 admitted for treatment in a designated hospital were retrospectively analyzed. Data were analyzed by SPSS statistical software. RESULTS: Pre-treatment T-cell subsets, total lymphocytes, red blood cell distribution width (RDW), eosinophils, and basophils were significantly lower than that of post-treatment, while the inflammatory indexes neutrophils, neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) levels, as well as red blood cell (RBC) and hemoglobin, were significantly reduced after treatment. The T-cell subsets, total lymphocytes, and basophils in severely and critically ill patients were significantly lower than those in moderately ill patients. Neutrophils, NLR, eosinophils, procalcitonin (PCT), and CRP was significantly higher in severely and critically ill patients than in moderately ill patients. CD3+, CD8+, total lymphocytes, platelets, and basophils in patients older than 50 were lower than that of those younger than 50, while neutrophils, NLR, CRP, and RDW in patients older than 50 were higher than that of younger than 50. There was a positive correlation among prothrombin time (PT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in severely and critically ill patients. CONCLUSIONS: T-cell subsets, lymphocyte count, RDW, neutrophils, eosinophils, NLR, CRP, PT, ALT, and AST are important indicators in the management especially for severely and critically ill patients with COVID-19.

The association of serum vitamin D-binding protein and 25-hydroxyvitamin D in pre-operative and post-operative colorectal cancer.

BACKGROUND: The association between vitamin D-binding protein (VDBP) and 25-hydroxyvitamin D (25 (OH)D) with colorectal cancer (CRC) is still ambiguous. This study was to further investigate the relationship between serum VDBP, 25 (OH)D levels and the clinical and pathological features of patients with CRC. METHODS: Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay were used to analyze the VDBP and 25(OH)D concentrations in serum. Pearson's correlation analysis was applied to evaluate the association between serum VDBP and 25(OH)D levels in CRC. Conditional logistic regression was performed to analyze the prediction value of serum VDBP or 25(OH)D as a risk factor for CRC. RESULTS: The serological levels of 25(OH)D in patients were significantly lower than in healthy individuals, while VDBP levels were significantly higher than in healthy controls. The serum VDBP in pre-operative was significantly lower than in post-operative samples, while the serum 25(OH)D from pre-operative patients was significantly higher than post-operative patients. Patients with tumors with higher stage and increased lymph node involvement had lower serum post-operative VDBP levels. In addition, our results showed that the pre-operative VDBP level is a risk factor of CRC. CONCLUSIONS: The levels of serum 25(OH)D and VDBP were both associated with CRC. Thus, serum 25(OH)D and VDBP levels might be of value in evaluating the pathogenesis and risk of CRC in the future. Moreover, serum VDBP or 25(OH)D levels were associated with patient's clinical and pathological features providing data for risk and prognostic prediction.

Discovery of Aberrant Alteration of Genome in Colorectal Cancer by Exome Sequencing.

BACKGROUND: This study analyzed multiple parameters including somatic single nucleotide variations (SNVs), Insertion/Deletions, significantly mutated genes (SMGs), copy number variations and frequently altered pathways aims to discover novel aberrances in the tumorigenesis of colorectal cancer (CRC). MATERIALS AND METHODS: Exome sequencing was performed on an Illumina platform to identify novel potential somatic variances in 34 paired tumor and adjacent normal tissues from 17 CRC patients. Results were compared with databases (dbSNP138, 1000 genomes SNP, Hapmap, Catalogue of Somatic Mutation of Cancer and ESP6500) and analyzed. MuSic software was used to identify SMGs. RESULTS: In total, 1,637 somatic SNVs in 17 analyzed tumors were identified. Only 7 SNVs were shared by more than 1 tumor, suggesting that over 99% of the analyzed SNVs were independent events. Mutation of KRAS p. G12D and ZNF717 p. L39V were the most common SNVs. Moreover, 10 SMGs namely KRAS, TP53, SMAD4, ZNF717, FBXW7, APC, ZNF493, CDR1, the Armadillo repeat containing 4 (ARMC4) and sulfate-modifying factor 2 (SUMF2) were found. Among those, ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 were novel frequent genes in CRC. For copy number variations analysis, gains in 10q25.3, 1p31.1, 1q44, 10q23.33, 11p15.4 and 20q13.33, and loss of 3q21.3 and 3q29 were frequent aberrations identified in our results. CONCLUSIONS: We frequently found novel genes ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 and gains in 10q25.3, which may be functional mutation in CRC. The high-frequency private events such as SNVs confirm the highly heterogeneous mutations found in CRCs. The mutated genes sites in different patients may vary significantly, which may also be more challenging for clinical treatment.

Expression of tetraspanins NET-6 and CD151 in breast cancer as a potential tumor biomarker.

Tetraspanins have been implicated in multiple biological functions including protein networking and cell signaling. NET-6 (TSPAN 13) has been demonstrated to be a tumor suppressor gene in breast cancer, while CD151 is more likely to act as an oncogene. However, the biological function of both proteins is still inconclusive. Immunohistochemistry was used to analyze the expression of NET-6 and CD151 proteins in breast tumors and benign epithelial cells. The cellular expression of both markers was correlated with HER2, ER, and PR status as well as tumor grade, Ki-67 scores, invasion, and metastasis. Expression of NET-6 and CD151 was variable both in tumors and in benign epithelial cells. Expression of NET-6 and CD151 was stronger in tumors than in benign epithelial cells. The expression of NET-6 was also stronger in HER2-negative, low-grade, lymphovascular invasion-negative, and non-metastatic breast tumors. There was no correlation between NET-6 expression and ER, or PR, or triple-negative status. There was no correlation between CD151 expression and HER2, ER, PR, or triple-negative status, tumor grade, or Ki-67 scores, invasion, and metastasis. The expression of tetraspanins NET-6 and CD151 may indicate an alteration of their biological function during neoplastic transformation. NET-6 expression in tumors might be a potential marker indicating the outcome of breast cancer.

Diagnostic and Prognostic Performance of Serum Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor 2, and Osteopontin for Gastrointestinal Cancers.

BACKGROUND: Biomarkers for early diagnosis and follow-up of cancers are still underutilized in clinical management. Thus, seeking new biomarkers with better sensitivity and specificity is still a challenge. VEGF, VEGFR2, and OPN are newly emerging biomarkers with clinical potential. METHODS: ELISA was used to analyze serum VEGF, VEGFR2, and OPN from 75 gastrointestinal cancer patients and 75 control subjects. The correlation of pre-operative serum VEGF, VEGFR2, and OPN levels with CEA, Ki-67 as well as clinical features (age, gender, tumor size, TNM stage, tumor stage, lymph node involvement, metastasis, and histological grading) in these patients. RESULTS: The pre-operative and post-operative serum VEGF and VEGFR2 levels and the post-operative OPN level in patients were significantly higher than in controls (p = 0.000, for all mentioned). The post-operative VEGF and OPN levels were significantly higher than that of pre-operative (p = 0.000 and 0.007, respectively). There was no correlation between pre-operative serum VEGF, VEGFR2, and OPN levels and serum CEA concentration. The pre-operative serum VEGF level was significantly correlated with the tumor Ki-67 scores; however, there was no correlation between serum VEGFR2 and OPN and Ki-67 scores. Univariate logistic regression analysis revealed that serum VEGF level was significantly higher in patients with advanced TNM (III - IV) stage and with lymph node involvement than in patients with low TNM stage (I - II) and with no lymph node involvement. High OPN level was correlated with metastasis. Multivariate logistic regression analysis results showed that serum VEGF and VEGFR2 were the two most important factors for the diagnosis of gastrointestinal cancers in this study (p = 0.000, for both). Combinatorial analysis of the biomarkers improved the performance of the assays. CONCLUSIONS: Serum VEGF and VEGFR2 are potential biomarkers for the diagnosis and prognosis evaluation of gastrointestinal cancers, while serum OPN is a potential biomarker for the prognostication of gastrointestinal cancers.

Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive Protein Levels in Acute Leukemia Patients.

BACKGROUND: Acute leukemia is a common hematologic malignancy with poorly differentiated leukocytes. Alteration of circulating vitamin D (VD) and its carrier vitamin D binding protein (VDBP) have been reported in certain types of cancers and may play a role in the course of the disease. Understanding of the status of serum VD and VDBP, as well as the acute phase protein C-reactive protein (CRP) levels in pre- and post-treatment of acute leukemia patients, may be helpful in the management of acute leukemia. METHODS: Enzyme linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and immunofluorescent assay were used to analyze the 25(OH) vitamin D (25(OH)D), VDBP, and CRP in the serum of a cohort of leukemia patients. RESULTS: Serum 25(OH)D levels in patients (pre- and post-treatment) were significantly lower than in control subjects. There was no significant difference in 25(OH)D levels between pre- and post-treatment. Serum VDBP level was raised in both pre- and post-treatment of acute leukemia patients, with that of pre-treatment being higher. The average serum VDBP was reduced in post-treatment; however, no significant difference was found. Elevated serum CRP levels in both pre- and post-treatment patient groups have been observed but were reduced significantly after treatment. Results also revealed that serum VDBP levels in acute myeloid leukemia patients were significantly higher than in acute lymphoid leukemia patients, while 25(OH)D levels in acute myeloid leukemia were significantly lower than in acute lymphoid leukemia. No significant difference between the serum CRP levels of acute myeloid leukemia and acute lymphoid leukemia was observed. CONCLUSIONS: Serum 25(OH)D, VDBP, and CRP may be used together and could be potential indicators of the disease course of acute leukemia and assist in its management which merits further investigation.

Differential cellular localization of CELSR2 and ING4 and correlations with hormone receptor status in breast cancer.

CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, its expression and function in cancer remain unknown. ING4 is a tumor suppresor encoded by the ING4 gene which inhibits cell growth. The expression of CELSR2 and ING4 in breast tumors and in benign epithelial cells have been analyzed and correlated with HER2, ER, and PR status. Immunohistochemistry was used to analyze the expression of CELSR2 and ING4 protein in breast tumors and benign epithelial cells. The differential cellular localization of both markers was analyzed and results were also correlated with HER2, ER, and PR status. CELSR2 and ING4 cytoplasmic expression was significantly stronger in tumors than in benign epithelial cells, while the nuclear expression of both markers was significantly stronger in benign epithelial cells than in tumors. When comparing the two markers in the same type of tissues, the nuclear expression of CELSR2 was significantly stronger than cytoplasmic in benign epithelial cells, while there was no significant difference in the cellular localization of CELSR2 in tumors. For ING4, the cytoplasmic expression was significantly stronger than nuclear expression in tumors, while in benign epithelial cells, ING4 was expressed at similar levels in both compartments. There was no correlation between CELSR2 expression and HER2, ER, and PR status in tumors. However, the cytoplasmic expression of ING4 was associated with HER2 positivity in tumors. Both CELSR2 and ING4 display increased cytoplasmic staining in breast cancer cells compared to benign epithelium, suggesting a possible role of both genes in the pathogenesis of human mammary neoplasia.