Fibrinogen beta chain may be a potential predict biomarker for pre-eclampsia: A preliminary study.

OBJECTIVE: There are no approaches for the early detection of pre-eclampsia (PE). Using parallel reaction monitoring proteomics, we investigated 79 maternal serum protein changes before PE onset and its predictive capability. METHODS: We conducted a nested case-control study with 60 PE patients and 60 normotensive pregnant women matched for age and gestational week. These differentially expressed proteins were quantified using the data-dependent acquisition (DDA) combined parallel response monitoring (PRM) approach, and a PE prediction model was developed using the least absolute shrinkage and selection operator (LASSO) regression. We further examined the link between these biomarkers and PE using bioinformatics. ELISA assay was used to investigate the expression and clinical significance of the critical variables. RESULTS: Among the 79 analyzed proteins, we identified 11 serum proteins with significantly abnormal expression. Fibrinogen beta chain (FGB) was likely connected with the progression of PE due to the positive correlation between their levels and those of hypertension and proteinuria. In addition, an early prediction model for PE with an AUC of 92% was developed using LASSO regression. CONCLUSION: Our research employs predictive algorithms and screens for relevant variables, which could result in a potential approach to enhancing PE prediction.

Ethanol promoting the upregulation of C-X-C Motif Chemokine Ligand 1（CXCL1） and C-X-C Motif Chemokine Ligand 6（CXCL6） in models of early alcoholic liver disease.

Alcoholic liver disease (ALD) denotes a series of liver diseases caused by ethanol. Recently, immune-related genes (IRGs) play increasingly crucial role in diseases. However, it's unclear the role of IRGs in ALD. Bioinformatic analysis was used to discern the core immune-related differential genes (IRDGs) in the present study. Subsequently, Cell Counting Kit-8 say, oil red O staining, and triglyceride detection were employed to explore optimal experimental conditions of establishing hepatocellular models of early ALD. Ultimately, real-time reverse transcription-PCR and immunohistochemistry/immunocytochemistry methods were adopted to verify the expressions of mRNA and proteins of core IRDGs, respectively. C-X-C Motif Chemokine Ligand 1 (Cxcl1) and Cxcl6 were regarded as core IRDGs via integrated bioinformatics analysis. Besides, Lieber Decarli Ethanol feeding and 200 mM and 300 mM ethanol stimulating L02 cells for 36 h can both successfully hepatocellular model. In ethanol groups, the levels of CXCL1 and CXCL6 mRNA were significantly upregulated than pair-fed groups (P < 0.0001). Also, immunohistochemistry revealed that positive particles of CXCL1 and CXCL6 in mice model of early ALD were obviously more than control groups (P < 0.0001). Besides, in L02 hepatocytes stimulated by ethanol, CXCL1 and CXCL6 mRNA were over-expressed, compared with normal L02 cells (P < 0.0001). Meanwhile, immunocytochemistry indicated that CXCL1 and CXCL6 proteins in hepatocellular model of early ALD were higher than normal L02 hepatocytes stimulus (P < 0.0001). Ethanol promoted the upregulation of Cxcl1 and Cxcl6 mRNA and proteins in models of early ALD, denoting their potentiality of acting as biomarkers of ALD.

Integrated Analyses Identify Key Molecules and Reveal the Potential Mechanism of miR-182-5p/FOXO1 Axis in Alcoholic Liver Disease.

Background: Alcoholic liver disease (ALD) is one of the most common chronic liver diseases worldwide. However, the potential molecular mechanism in ALD development remains unclear. The objective of this work was to identify key molecules and demonstrate the underlying regulatory mechanisms. Methods: RNA-seq datasets were obtained from Gene Expression Omnibus (GEO), and key molecules in ALD development were identified with bioinformatics analysis. Alcoholic liver disease mouse and cell models were constructed using Lieber-DeCarli diets and alcohol medium, respectively. Quantitative real-time PCR and Western blotting were conducted to confirm the differential expression level. Dual-luciferase reporter assays were performed to explore the targeting regulatory relationship. Overexpression and knockdown experiments were applied to reveal the potential molecular mechanism in ALD development. Results: Between ALD patients and healthy controls, a total of 416 genes and 21 microRNAs (miRNAs) with significantly differential expression were screened. A comprehensive miRNA-mRNA network was established; within this network, the miR-182-5p/FOXO1 axis was considered a significant pathway in ALD lipid metabolism. Mouse and cell experiments validated that miR-182-5p was substantially higher in ALD than in normal livers, whereas the expression of FOXO1 was dramatically decreased by alcohol consumption (P < 0.05). Next, dual-luciferase reporter assays demonstrated that miR-182-5p directly targets the binding site of the FOXO1 3'UTR and inhibits its mRNA and protein expression. In addition, miR-182-5p was found to promote hepatic lipid accumulation via targeting the FOXO1 signaling pathway, and inhibition of the miR-182-5p/FOXO1 axis improved hepatic triglyceride (TG) deposition in ALD by regulating downstream genes involved in lipid metabolism. Conclusion: In summary, key molecules were identified in ALD development and a comprehensive miRNA-mRNA network was established. Meanwhile, our results suggested that miR-182-5p significantly increases lipid accumulation in ALD by targeting FOXO1, thereby providing novel scientific insights and potential therapeutic targets for ALD.

Prognostic value of circulating tumor cells in patients with bladder cancer: A meta-analysis.

BACKGROUND: Circulating tumor cells (CTCs) have been considered diagnostic and prognostic biomarkers for urothelial cancer. However, the prognostic role of CTCs in bladder cancer (BC) remains controversial. Here, we conducted a meta-analysis to evaluate the prognostic significance of CTCs for patients with BC. METHODS: All studies relevant to this topic were searched in the PubMed, Embase, and Web of Science databases. The hazard ratio (HR) and 95% confidence interval (95% CI) were set as effect measures. The outcomes were overall survival (OS), cancer-free survival (CSS), progression-free survival (PFS)/time to progression (TTP), and disease-free survival (DFS)/recurrence-free survival (RFS)/time to first recurrence (TFR). All analyses were conducted in STATA 15.1. RESULTS: Eleven eligible studies comprising 1,062 patients with BC were included in this meta-analysis. Overall analyses showed that CTC-positive patients had poorer survival (OS: HR 3.88, 95% CI 2.52-5.96, p < 0.001; CSS: HR 3.89, 95% CI 2.15-7.04, p < 0.001) and more aggressive progression (PFS/TTP: HR 5.92, 95% CI 3.75-9.35, p < 0.001; DFS/RFS/TFR: HR 4.57, 95% CI 3.34-6.25, p < 0.001) than CTC-negative patients. Subgroup analyses according to the number of patients, detection method, positivity rate, and follow-up time revealed that the presence of CTCs predicted a high risk of mortality and disease progression in most subgroups. CONCLUSION: The meta-analysis confirmed that CTCs are a promising prognostic biomarker of poor survival and aggressive tumor progression for patients with BC. PROSPERO REGISTRATION NUMBER: CRD42021224865.

Long noncoding RNAs as biomarkers for the diagnosis of hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are often aberrantly expressed in hepatocellular carcinoma (HCC). The role of lncRNAs in the diagnosis of HCC has attracted increasing attention. Hence, we performed a meta-analysis based on current studies to assess the diagnostic value of lncRNAs for HCC. METHODS: A systematic search was performed using PubMed, Web of Science, and Embase databases for relevant studies. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). A fixed-effect model was used if the value of I2 statistics < 50%; otherwise, a bivariate random effects model was applied (I2 ≥ 50%). In addition, subgroup analysis and meta-regression analysis were conducted to explore the sources of heterogeneity. Statistical analyses were based on Meta-Disc statistical software (Version 1.4) and STATA software (Version 15.1). RESULTS: A total of 52 studies in 20 related articles were selected for this meta-analysis, including 4930 patients and 4614 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.85 [95% confidence interval (CI) 0.82-0.88], 0.76 (95% CI 0.73-0.80), 3.6 (95% CI 3.1-4.2), 0.19 (95% CI 0.16-0.24), 19 (95% CI 14-26), and 0.88 (95% CI 0.85-0.91), respectively. The publication bias was evaluated by the Deek's funnel plot in our meta-analysis. CONCLUSIONS: LncRNAs can serve as feasible HCC diagnostic biomarkers. However, further studies are necessary to confirm its diagnostic and clinical value.

Exploration of a Robust and Prognostic Immune Related Gene Signature for Cervical Squamous Cell Carcinoma.

Background: Cervical squamous cell carcinoma (CESC) is one of the most frequent malignancies in women worldwide. The level of immune cell infiltration and immune-related genes (IRGs) can significantly affect the prognosis and immunotherapy of CESC patients. Thus, this study aimed to identify an immune-related prognostic signature for CESC. Methods: TCGA-CESC cohorts, obtained from TCGA database, were divided into the training group and testing group; while GSE44001 dataset from GEO database was viewed as external validation group. ESTIMATE algorithm was applied to evaluate the infiltration levels of immune cells of CESC patients. IRGs were screened out through weighted gene co-expression network analysis (WGCNA). A multi-gene prognostic signature based on IRGs was constructed using LASSO penalized Cox proportional hazards regression, which was validated through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. The abundance of immune cells was calculated using ssGSEA algorithm in the ImmuCellAI database, and the response to immunotherapy was evaluated using immunophenoscore (IPS) analysis and the TIDE algorithm. Results: In TCGA-CESC cohorts, higher levels of immune cell infiltration were closely associated with better prognoses. Moreover, a prognostic signature was constructed using three IRGs. Based on this given signature, Kaplan-Meier analysis suggested the significant differences in overall survival (OS) and the ROC analysis demonstrated its robust predictive potential for CESC prognosis, further confirmed by internal and external validation. Additionally, multivariate Cox analysis revealed that the three IRGs signature served as an independent prognostic factor for CESC. In the three-IRGs signature low-risk group, the infiltrating immune cells (B cells, CD4/8 + T cells, cytotoxic T cells, macrophages and so on) were much more abundant than that in high-risk group. Ultimately, IPS and TIDE analyses showed that low-risk CESC patients appeared to present with a better response to immunotherapy and a better prognosis than high-risk patients. Conclusion: The present prognostic signature based on three IRGs (CD3E, CD3D, LCK) was not only reliable for survival prediction but efficient to predict the clinical response to immunotherapy for CESC patients, which might assist in guiding more precise individual treatment in the future.

Silencing of Long Non-coding RNA ENST00000606790.1 Inhibits the Malignant Behaviors of Papillary Thyroid Carcinoma through the PI3K/AKT Pathway.

PURPOSE: This study aimed to investigate the role and mechanism of lncRNA ENST00000606790.1 (ENST) in promoting the progression of papillary thyroid carcinoma (PTC). METHODS: The expression of ENST in human PTC and normal para-cancerous thyroid (NPTC) tissues or cell lines was determined by RT-qPCR. Cell growth was determined by CCK8 assay. Cell colony formation was determined by cell colony formation assay. Cell cycle analysis was performed by staining cells with PI (Propidium Iodide). Cell invasion was assessed by transwell assay. Protein expression was examined by western-blot. siRNA was constructed to inhibit the expression of ENST. 740-Y-P was used to activate PI3K. The correlation between ENST expression and clinical outcomes was analyzed. RESULTS: ENST was significantly up-regulated in PTC tissues or PTC cell lines (PTC and IHH4 cell lines), compared to NPTC tissues or normal cell lines, respectively. High expression of ENST was strongly correlated to lymph node metastasis and tumor size at diagnosis. Silencing of ENST significantly inhibited cell growth and colony formation, arrested the cell cycle at G2/M phase, upregulated the expression of CHK1, downregulated the expression of CDC25C, and inhibited cell invasion. Silencing of ENST significantly down-regulated the expression of PI3K, p-PI3K, AKT, and p-AKT in IHH4 cells. Furthermore, treatment with the PI3K activator  740-Y-P partially abolished the effect of silencing of ENST on PTC cells. CONCLUSIONS: Overall, our results demonstrated that ENST can promote PTC progression by activating the PI3K/AKT signaling pathway, suggesting that ENST can serve as a potential biomarker and new therapeutic target for patients with PTC.

A Nomogram for the Prediction of Progression and Overall Survival in Childhood Acute Lymphoblastic Leukemia.

Background: Advances in treatment and supportive care have significantly improved the overall survival (OS) of pediatric patients with acute lymphoblastic leukemia (ALL). However, there is a large number of these patients who continue to relapse after receiving standard treatment. Accurate identification of patients at high risk of relapse and targeted therapy may significantly improve their prognosis. Therefore, the aim of this study was to identify significant prognostic factors for pediatric ALL and establish a novel nomogram for the prediction of survival. Methods: The ALL clinical data of Phases I and II of the Therapeutic Applicable Research to Generate Effective Treatments (TARGET) project were merged and randomly divided into training and validation groups. The LASSO regression model was used to select the specific factors related to the OS of the training group and generate prognostic nomograms according to the selected characteristics. The predictive accuracy of the nomogram for OS was verified using the concordance index of the training and validation groups, the area under the receiver operating characteristic curve for prognostic diagnosis, and the calibration curve. Results: A total of 1,000 children with ALL were included in the TARGET project. Of those, 489 patients had complete follow-up data for further analysis. The data were randomly divided into the training group (n = 345) and the validation group (n = 144). Seven clinical characteristics, namely age at diagnosis, peripheral white blood cells, bone marrow and CNS site of relapse, ETV6/RUNX1 fusion, TCF3/PBX1, and BCR/ABL1 status, were selected to construct the nomogram. The concordance indices of the training and validation groups were 0.809 (95% confidence interval: 0.766-0.852) and 0.826 (95% confidence interval: 0.767-0.885), respectively. The areas under the receiver operating characteristic curve of the 3-year, 5-year, and 10-year OS in the training group were 0.804, 0.848, and 0.885, respectively, while that of the validation group were 0.777, 0.825, and 0.863, respectively. Moreover, the calibration curves demonstrated a favorable consistency between the predicted and actual survival probabilities. Conclusions: Independent predictors of OS in children with ALL included age at diagnosis, white blood cells, bone marrow site of relapse, CNS site of relapse, ETV6/RUNX1 fusion, TCF3/PBX1, and BCR/ABL1 status. The nomograms developed using these high-risk factors can more simply, accurately, and quantitatively predict the survival of children, and improve treatment and prognosis.

Overexpression of novel long intergenic non­coding RNA LINC02454 is associated with a poor prognosis in papillary thyroid cancer.

It has been revealed from microarray data analysis that long intergenic non­coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription­quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The expression level of LINC02454 was significantly increased in PTC tissues (P=0.0011) and was significantly associated with a larger tumor size, T stage, an advanced TNM stage and an increased lymph node metastasis (P<0.05), which was consistent with that in the TCGA and GSE66783 cohort. High expression levels of LINC02454 were observed in patients with PTC that also had BRAF mutations (P<0.001), and were significantly associated with a poorer disease­free survival in the TCGA cohort (P<0.05). Functional enrichment analysis indicated that LINC02454­related genes were significantly enriched in Gene Ontology terms, such as 'positive regulation of cell proliferation', 'positive regulation of cell division' and 'cell adhesion', and the following Kyoto Encyclopedia of Genes and Genomes pathways: 'Pathways in cancer' 'proteoglycans in cancer' and 'ECM­receptor interaction'. In vitro, the knockdown of LINC02454 markedly arrested the cells in the G0/G1 phase of the cell cycle, and also led to an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.

The value of microRNAs as the novel biomarkers for colorectal cancer diagnosis: A meta-analysis.

BACKGROUND: Numerous studies have reported that microRNAs (miRNAs) hold great potential as the biomarkers for colorectal cancer (CRC). However, inconsistent results have made it challenging to evaluate their diagnostic performance. Thus, the aim of this meta-analysis was to systematically assess the pooled efficacy of miRNAs for CRC diagnosis. METHODS: A search for eligible studies up to October 30, 2019 was conducted using PubMed, Web of Science and EMBASE databases. A random-effects model was used to evaluate the pooled sensitivity and specificity. The summary receiver operator characteristic (SROC) curve and area under the curve (AUC) were calculated to assess the overall diagnostic efficacy. RESULTS: A total of 3258 CRC patients and 2683 healthy controls were identified in 35 included studies. The overall diagnostic accuracy was as follows: sensitivity, 0.80 [95 % confidence interval (CI) 0.75-0.83]; specificity, 0.80 (95 % CI, 0.75-0.84); positive likelihood ratio (PLR), 4.0 (95 % CI, 3.2-5.0); negative likelihood ratio (NLR), 0.26 (95 % CI, 0.21-0.31); diagnostic odds ratio (DOR), 16 (95 % CI, 11-23); and AUC, 0.87 (95 % CI, 0.83-0.89). CONCLUSION: The results indicated that miRNAs, particularly serum-derived miRNAs, can serve as the powerful and promising biomarkers for early CRC screening.

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. METHODS: Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. RESULTS: Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. CONCLUSIONS: Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.

Circulating MicroRNAs as Promising Diagnostic Biomarkers for Patients With Glioma: A Meta-Analysis.

Backgrounds and Purpose: Currently, circulating microRNAs (miRNAs) are considered to be non-invasive diagnostic biomarkers in a broad range of tumors. Nevertheless, so far, miRNAs have not been fully applied to the clinic for routine screening in glioma patients. Thus, our goal is to evaluate the diagnostic performance of circulating miRNAs for gliomas via a meta-analysis. The present study is registered on the PROSPERO website, with the number CRD42020195883. Methods: Literature retrieval was implemented in the PubMed, Embase, and Web of Science databases using the established search strategy. We pooled the sensitivity, specificity, and its 95% confidence intervals (CIs) for the included studies using the Stata 14.0 software. In addition, the heterogeneity between studies was assessed via the Q statistics and I 2 values calculated by a Chi-square test. A bivariate random effects model was selected due to significant heterogeneity. Specifically, for exploring the factors influencing the heterogeneity, we implemented subgroup and meta-regression analyses. Ultimately, a Deek's funnel plot asymmetry test was used to estimate the potential publication bias. Results: A total of 18 articles covering 24 studies were included, containing 2,170 glioma patients and 1,456 healthy participants. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.84 (95%CI: 0.79-0.87), 0.84 (95%CI: 0.80-0.88), 5.3 (95%CI: 4.1-6.8), 0.19 (95%CI: 0.15-0.25), 27 (95%CI: 18-41), and 0.91 (95%CI: 0.88-0.93), respectively. Additionally, the findings revealed that serum miRNAs and miRNA panels presented superior diagnostic performance. Conclusion: Thus, circulating miRNAs have the potential to serve as diagnostic biomarkers for gliomas, but need to be verified via a large pool of prospective studies. Additionally, specific miRNAs still need to be elucidated in the diagnosis of a glioma, especially in the early screening stage. The findings may provide diagnostic and therapeutic strategies for the glioma population.

LncRNA ENST00000539653 acts as an oncogenic factor via MAPK signalling in papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most frequent type of thyroid malignancy. In this study, we investigated the mechanisms whereby long non-coding RNAs (lncRNAs) are associated with PTC pathogenesis. METHODS: Microarray analysis was used to determine differentially expressed lncRNAs between paired PTC tissues and normal adjacent thyroid tissues. Quantitative RT-PCR was used for validation in 86 PTC cases. Small interfering RNA (siRNA) transfection assays were then performed to assess how a novel lncRNA affected key proliferation and cell death pathways in IHH4 PTC cells. RESULTS: We identified 1878 differentially expressed lncRNAs versus matched control samples (fold change ≥2.0, P < 0.05), of which 429 were upregulated and 1449 were downregulated. ENST00000539653.1 (ENS-653), one of the top hits in this microarray, was selected for further study. Higher ENS-653 expression was observed in PTC tissue samples versus adjacent normal tissues, and was associated with a larger tumor size and a more advanced clinical stage. In the Cancer Genome Atlas (TCGA) PTC cohort, higher ENS-653 expression was correlated with more frequent BRAF (V600E) mutation and poorer disease-free survival. Furthermore, ENS-653 downregulation reduced the proliferation of PTC cells and led to G1-S arrest, but had no impact on apoptosis. ENS-653 downregulation also inactivated ERK1/2 and ERK5, causing partial MAPK cascade suppression. CONCLUSION: ENS-653 exhibits oncogenic properties in PTC, and could be a diagnostic and/or prognostic PTC biomarker, in addition to possibly being a future target for therapy.

Integrated bioinformatics analysis reveals that the expression of cathepsin S is associated with lymph node metastasis and poor prognosis in papillary thyroid cancer.

The prognosis of the majority of patients with papillary thyroid cancer (PTC) is excellent, although there are patients who experience disease recurrence and progression. The aim of the present study was to identify potential prognostic risk markers in PTC. Differentially expressed genes (DEGs), identified from four Genome Expression Omnibus cohorts were subjected to functional enrichment analyses with Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genome pathways. Hub genes, filtered from cytoHubba, were validated using the The Cancer Genome Atlas (TCGA) cohort, and their associations with clinicopathological features and prognosis were analyzed. A total of 277 DEGs were identified following data preprocessing. DEGs were primarily enriched in 'small cell lung cancer', 'ECM-receptor interaction', 'pathways in cancer'and 'tyrosine metabolism'. Hub genes [APOE, cathepsin S (CTSS), insulin receptor substrate 1 (IRS1), KIT, LGALS3, RUNX2 and TGFBR1] were extracted from cytoHubba. Their expression in the TCGA cohort was consistent with that in the GEO cohorts. CTSS (P=0.006) and IRS1 (P=0.005) were associated with disease­free survival, as determined using the Kaplan-Meier analysis. CTSS was an independent risk factor for poor disease­free survival (HR, 2.649; 95% CI, 1.095-6.409; P=0.031). Patients with high expression of CTSS exhibited different histological types (increased tall-cell subtype and reduced follicular subtype; P<0.001), more frequent lymph node metastasis (P<0.001) and advanced tumor-node-metastasis stages (P=0.049) compared with the low-expression group. High expression of CTSS was independently associated with lymph node metastasis (OR, 2.015; 95% CI, 1.225-3.315; P=0.006). Therefore, CTSS may serve as a predictive risk marker for the progression and prognosis of PTC.

The effect of vitamin D supplementation on thyroid autoantibody levels in the treatment of autoimmune thyroiditis: a systematic review and a meta-analysis.

PURPOSE: Although observational studies suggested that vitamin D plays a role in autoimmune thyroiditis (AIT), intervention trials yielded inconsistent findings. We therefore conducted a systematic review and a meta-analysis to evaluate the effects of Vitamin D on decreasing autoantibodies in patients with AIT. METHOD: We identified all studies that assessed the changes of TPO-Ab and Tg-Ab in patients with AIT under the treatment of vitamin D from PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and VIP Database. RESULTS: Six randomized controlled trials (RCTs) were included in this systematic review representing a total of 344 patients with AIT. The results showed that Vitamin D supplementation significantly dropped TPO-Ab titers [three studies, random effects standardized mean difference (SMD): -1.11, 95% CI -1.52 to -0.70, P < 0.01] at six months, but not at no more than 3 months [random effects SMD: -0.12, 95% CI: -0.69 to 0.44, P = 0.67]. As compared with control group, participants who received vitamin D supplementation demonstrated significantly lower Tg-Ab [random effects SMD: -0.55, 95% CI: -1.05 to -0.04, P = 0.033]. In addition, no serious adverse effect was reported. CONCLUSIONS: The current evidence suggests that vitamin D supplementation could decrease serum TPO-Ab and Tg-Ab titers of patients with AIT in the short-term (about six months). More high quality studies are needed to further confirm the effects, especially the long-term effects of Vitamin D supplementation on thyroid autoantibodies levels in the treatment of AIT.

Association of thyroid nodules with adiposity: a community-based cross-sectional study in China.

BACKGROUND: The association between thyroid nodules and adiposity remains controversial. We performed a cross-sectional, community-based study to examine whether thyroid nodules are associated with overweight and obesity, as defined with body mass index (BMI) and waist circumference. METHODS: The study included 1482 subjects (≥20 years of age; residing in Nanjing, China) receiving questionnaire interview, anthropometric measurements, laboratory tests and thyroid ultrasonography in 2009-2010. Overweight and obesity were defined as BMI ≥24 and ≥28 kg/m2, respectively. Central obesity was defined as waist circumference at ≥90 cm in men and ≥80 cm in women. A sensitivity analysis was conducted using the American Diabetes Association (ADA) criteria for overweight and obesity (BMI ≥ 23 and ≥25 kg/m2). RESULTS: Thyroid nodules were identified in 12.6% of the subjects. A greater proportion of the subjects with thyroid nodules had a BMI at ≥24 kg/m2 (51.9% vs. 40.5% in those without thyroid nodules, P = 0.003) and central obesity (43.3% vs. 24.2%, P < 0.001). After adjustment for other confounders, central obesity was still associated with significantly elevated risk of thyroid nodules (OR 1.62, 95%CI 1.14-2.28), whereas obesity/overweight based on BMI was not in both the main analysis and sensitivity analysis with the alternative criteria. In the subgroup analysis, BMI ≥24 kg/m2 (OR 1.61, 95%CI 1.01-2.54), as well as BMI ≥25 kg/m2 (OR 1.95, 95%CI 1.14-3.34), was significantly associated with higher risk of thyroid nodules among women. Using the ADA criteria, overweight and obesity were associated with thyroid nodules (OR 5.59, 95%CI 1.39-22.51 and 5.15, 95%CI 1.30-20.37) in thyroid-stimulating hormone (TSH) > 4.2 mIU/L subgroup. Central obesity correlated with higher risk of thyroid nodules regardless of age (< 50 years: OR 1.87, 95%CI 1.05-3.32: ≥50 years: OR 1.54, 95%CI 1.00-2.37) and in the following subgroups: men (OR 1.91, 95%CI 1.14-3.20), TSH > 4.2 mIU/L (OR 3.05, 95%CI 1.01-9.22), and urine iodine ≥200 µg/L (OR 1.79, 95%CI 1.14-2.81). CONCLUSION: Waist circumference is superior to BMI for assessing risk of thyroid nodules in Chinese subjects.

[Analyzing the occupational hazard of 258 construction projects of Shunde in 2010 and 2011].

OBJECTIVE: To understand the changing trend of occupational hazard of industries in Shunde area and to provide the scientific evidence for the prevention of occupational diseases. METHODS: The pre-evaluation of occupational hazard was carried out for the construction projects. The data about employee number scale, industry species, occupational hazard factors, hazard levels and prevention measures for construction projects were collected and analyzed. The data of Shunde Occupational Health Survey in 2011 served as the control data. RESULTS: There were 258 construction projects in 2010 and 2011, in which the proportions of medium and large scales increased to 8.1% and 2.4% respectively, the proportions of the furniture and chemical industries decreased from 25.6% or/and 5.1% to 2.7% or/and 1.8%, the proportions of the high-tech industries increased from 1.8% to 9.2%. The proportions of the projects with serious, medium and slight occupational hazard levels were 4.3%, 67.8% and 27.9%, respectively. The proportions of the projects with harmful chemicals, dusts and physical factors were 34.2%, 46.8%, 42.6%, respectively. CONCLUSION: The feature of occupational hazard in Shunde industries has changed at upgrading stage. We should pay attention to the prevention of occupational diseases in high-tech industries.