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Objective·To examine the level change of serum renalase in the patients with acute ischemic stroke (AIS), and analyze its role in evaluating disease.Methods·A total of 118 AIS patients admitted to the Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2020 to November 2021 were enrolled in the case group (AIS group). The patients were assessed for neurological deficits according to the National Institutes of Health Stroke Scale (NIHSS), and were classified as mild and moderate-severe neurological deficits. Another 133 healthy people who participated in physical examination in the physical examination center of the hospital during the same period were selected as the control group. The serum renalase levels of the two groups were detected by ELISA. Spearman's rank correlation analysis was used to evaluate the correlation between the levels of serum renalase and gender, age, fasting blood glucose, blood lipids and NIHSS scores in the patient with AIS. The predictive value of renalase expression level in AIS diagnosis was analyzed by receiver operator characteristic (ROC) curve. The factors that were statistically significant in the results of the univariate Logistic regression analysis were included in the multivariate Logistic regression model.Results·The level of serum renalase in the AIS group was 2 960.01 (1 557.99, 4 053.70) pg/mL, which was higher than 821.02 (391.29, 1 752.70) pg/mL in the control group, with a statistically significant difference (P=0.000). Spearman's rank correlation analysis showed that the levels of serum renalase in the patients with AIS were negatively correlated with the NIHSS scores (r=-0.216, P=0.019), positively correlated with the serum fasting glucose (r=0.200, P=0.030), and not significantly correlated with gender, age, low-density lipoprotein levels, total cholesterol levels, and the presence of hypertension, diabetes, or coronary heart disease. Serum renalase levels were higher in the AIS with mild neurological deficit patients than those in the moderate-severe deficit patients, and the difference was statistically significant (P=0.034). The ROC curve showed that the cut-off value of serum renalase level to diagnose AIS was 1 856.49 pg/mL, the area under the curve was 0.777±0.030 and its 95%CI was 0.718‒0.836 (P=0.000). Multivariate Logistic regression analysis showed that elevated serum renalase level [>1 856.49 pg/mL, odds ratio (OR)=6.980, P=0.000], hypertension (OR=5.382, P=0.000), and diabetes (OR=2.453, P=0.040) were risk factors for AIS.Conclusion·Serum renalase level is significantly elevated in AIS patients, and negatively correlated with NIHSS score. Serum renalase might be a potential biomarker for the auxiliary diagnosis and assessment of AIS, providing new ideas for the assessment of stroke disease progression and precise treatment.

Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRβ gene. To explore potential impact of genetic background in the BIOMED-2 test, we analyzed TCRβ sequences of 21 healthy individuals and two TCL patients. This analysis suggests that genetic variations in the BIOMED-2 primer sites could not explain the difference in sensitivity. The BIOMED-2 test results of the two TCL patients were positive and negative, respectively. Interestingly, a higher percentage (>81%) of non-recombined TCRβ sequences was observed in the test-negative patient than those of the test-positive patient and all healthy individuals (13~66%). The result suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRβ sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.

Introduction: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM.Methods: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene.Results: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments.Discussion: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM. [ABSTRACT FROM AUTHOR]

Increased physical activity has been associated with reduced risks of various physical and mental conditions. However, the association between physical activity and liver health in the Chinese general adult population is not clear. This study investigated whether physical activity, stratified by intensity (i.e. walking (light), moderate-to-vigorous), was associated with alanine aminotransferase (ALT) level in middle-aged and older Chinese adults. Two independent surveys of urban (n = 5,824, males 44%, mean (standard deviation) age 52 (10) years) and rural populations (n = 20,269, males 41%, mean (standard deviation) age 51 (10) years) were undertaken. Physical activity was measured using the International Physical Activity Questionnaire, and in metabolic equivalents of task (MET) × minutes. Elevated serum level of ALT, a clinical surrogate of abnormal liver function, was defined as >40 IU/L (males) and >30 IU/L (females). Multivariable regression models were used. Amount of moderate-to-vigorous activity was inversely associated with serum level of ALT (β = −0.147 per 1k MET-minutes, p < 0.001), whereas walking was not associated. People who reached the lower limit of WHO recommendation (≥600 MET-minutes per week) had a reduced odds of ALT elevation, compared to those who did not (adjusted odds ratio: 0.85 95%CI (0.76, 0.95)). Meeting the moderate-to-vigorous recommendations for physical activity in adults may be associated with decreased likelihood of abnormal liver function both in Chinese urban and rural populations. Promoting such activities could be a low-cost strategy in maintaining liver health as well as providing many other health-related benefits. [ABSTRACT FROM AUTHOR]

Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87‐MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down‐regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual‐luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at −236 to ‐230 bp and −1354 to ‐1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells. [ABSTRACT FROM AUTHOR]

• PPAs contents are positively related to the amount of PAs exposure. • PPAs form faster but cleared slower in liver than in serum. • PPAs clear slowly in several extra-hepatic organs, suggesting the potential extra-hepatic toxicities of PAs. Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T 1/2ke∼ 184.6 h, ∼7.7 days) than in serum (T 1/2ke ∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV‐miR‐BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR‐BART7‐3p and miR‐BART13‐3p. Plasma levels of EBV DNA, miR‐BART7‐3p, and miR‐BART13‐3p were examined by quantitative PCR in 483 treatment‐naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow‐up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR‐BART7‐3p, 0.973 for miR‐BART13‐3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above‐median miR‐BART7‐3p and EBV DNA were independent risk for shorter distant metastasis‐free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44‐5.97, P =.003; HR = 2.27, 95% CI, 1.26‐4.10, P =.006) in multivariate Cox regression. Epstein‐Barr virus DNA, miR‐BART7‐3p, and miR‐BART13‐3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR‐BART7‐3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89‐9.01, P <.001; HR = 2.14, 95% CI, 1.04‐4.42, P =.039). The 4‐year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR‐BART7‐3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR‐BART7‐3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR‐BART7‐3p and EBV DNA after radiotherapy (P <.001). Circulating levels of miR‐BART7‐3p and miR‐BART13‐3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR‐BART7‐3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between nadir platelet count and acute kidney injury (AKI) or 28-day all-cause mortality induced by hemorrhagic shock (HS), and to determine the cutoff value of nadir platelet count in HS clinical practice. This retrospective study included hospitalized patients enrolled in a tertiary-care teaching hospital from January 1, 2010 to December 31, 2015. Clinical data from HS admitted to the intensive care unit (ICU) were evaluated. Nadir platelet count was defined as the lowest values in the first 48 h. Multivariate logistic regression and Cox proportional hazards regression were used to assess the correlation between nadir platelet count and AKI or 28-day all-cause mortality induced by HS, respectively; the area under receiver operating characteristic (AU-ROC) and Youde's index were used to determine the optimal cutoff value of nadir platelet count. Kaplan-Meier's method and log-rank test were assessed for the 28-day all-cause mortality in AKI and non-AKI groups. Of 1589 patients screened, 84 patients (mean age,37.1 years; 58 males) were included in the primary analysis in which 30 patients with AKI. Multiple logistic results indicated that nadir platelet count was a risk factor of AKI (OR = 0.71,95% confidence interval [CI] 0.54–0.93, P < 0.05). Cox regression analysis revealed that nadir platelet count was independent risk factors for 28-day all-cause mortality (Hazard ratios [HR]0.89,95%CI 0.76–0.99, P < 0.05). Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with AKI than non-AKI (P < 0.001).These results suggest that nadir platelet count in the first 48 h is a new biomarker for AKI and 28-day all-cause mortality induced by HS. Moreover, the risk for AKI and 28-day all-cause mortality in HS patients decreased by 29% and 11%, respectively, for every 10 × 109/L increase in platelet count. Additional studies are needed to investigate whether elevation of nadir platelet count reduces the risk in different genders. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether the presence of interictal scalp EEG high frequency oscillations (HFOs) in children with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) can predict seizure and cognitive outcome after steroid therapy.Methods: Twenty-two children with CSWS were prospectively enrolled and received methylprednisolone therapy. Interictal scalp HFOs, spike wave index (SWI) and intelligence quotient (IQ) were assessed before and after the treatment. The children were divided into two groups based on the early seizure reduction ratio at 2 weeks (≥50%, "response group"; otherwise "non-response group"). The "response group" was further divided into two subgroups ("relapse" and "non-relapse" subgroups) according to the late seizure outcome (after 3 months).Results: Interictal HFOs and electrical status epilepticus in sleep (ESES) (defined as SWI ≥ 85%) were detected in all children at the baseline. In the response with relapse group (n = 11), the detection ratio of HFOs was significantly higher than that of ESES at 2 weeks (81.2 vs. 27.3%), 3 months (90.9 vs. 36.4%), and 6 months (100 vs. 54.5%) post-therapy. In the non-response group (n = 4), both HFOs and ESES persisted in all children. The average IQ improved significantly only in the response with non-relapse group. The persistence of HFOs negatively correlated with both the average IQ, yet the persistence of ESES did not.Conclusion: Interictal scalp HFOs may be a favorable non-invasive biomarker of predicting seizure and cognitive outcome in CSWS. [ABSTRACT FROM AUTHOR]

Introduction Stent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention. Materials and methods From January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission. Results The incidence of definite and probable ST at 2 years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p = 0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14–3.73, p = 0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03–5.06, p = 0.041), but not in those with stable coronary artery disease ( p = 0.331), and tended to be associated with older age. Conclusions Plasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population. [ABSTRACT FROM AUTHOR]

The colorectal cancer ( CRC) is one of the leading causes of cancer-related death worldwide, but the pathogenesis of CRC remains not well-known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lnc RNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lnc RNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome-wide comprehensive analysis of lnc RNAs profiling and clinical relevance to identify novel lnc RNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas ( TCGA) and Gene Expression Omnibus ( GEO) were annotated and analyzed to find differentially expressed lnc RNAs in CRC. Analysis of these datasets revealed that hundreds of lnc RNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lnc RNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lnc RNAs expression levels are significantly associated with CRC patients overall and recurrence-free survivals, such as H19, LEF1- AS1, and RP11-296E3.2. Furthermore, we identified one liver metastasis-associated lnc RNA termed LUCAT1 in CRC by analyzing lnc RNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss-of-function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lnc RNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC. [ABSTRACT FROM AUTHOR]

Although chemotherapy plus PD-1 blockade (chemo+anti-PD-1) has become the standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), reliable biomarkers for this regimen are lacking. Here we perform whole-exome sequencing on tumor samples from 486 patients of the JUPITER-06 study and develop a copy number alteration-corrected tumor mutational burden that depicts immunogenicity more precisely and predicts chemo+anti-PD-1 efficacy. We identify several other favorable immunogenic features (e.g., HLA-I/II diversity) and risk oncogenic alterations (e.g., PIK3CA and TET2 mutation) associated with chemo+anti-PD-1 efficacy. An esophageal cancer genome-based immuno-oncology classification (EGIC) scheme incorporating these immunogenic features and oncogenic alterations is established. Chemo+anti-PD-1 achieves significant survival improvements in EGIC1 (immunogenic feature-favorable and oncogenic alteration-negative) and EGIC2 (either immunogenic feature-favorable or oncogenic alteration-negative) subgroups, but not the EGIC3 subgroup (immunogenic feature-unfavorable and oncogenic alteration-positive). Thus, EGIC may guide future individualized treatment strategies and inform mechanistic biomarker research for chemo+anti-PD-1 treatment in patients with advanced ESCC. [Display omitted] • Prospectively collected ESCC specimens from a phase 3 trial on immunochemotherapy • CNA-corrected TMB predicts benefit from chemotherapy plus anti-PD-1 • Identified resistance genomic events to immunochemotherapy in ESCC • Immuno-oncogenic classification sheds light on individualized treatment in ESCC Chen et al. perform genomic analyses on prospectively collected ESCC specimens from the JUPITER-06 trial and identify genomic immune-oncogenic characteristics associated with benefits from chemotherapy plus anti-PD-1 in ESCC. The esophageal cancer genome-based immuno-oncogenic classification scheme developed based on these characteristics sheds light on individualized treatment for ESCC patients. [ABSTRACT FROM AUTHOR]

Circular RNAs (circ RNAs) are associated with cancer progression and metastasis, although little is known about their role in lung adenocarcinoma ( LAC). In the present study, microarrays were first used to screen for tumour-specific circ RNA candidates in LAC tissue. Thirty-nine circ RNAs were found to be up-regulated and 20 were down-regulated (fold change > 2.0). Among them, hsa_circ_0013958 was further confirmed to be up-regulated in all of the LAC tissues, cells and plasma. In addition, hsa_circ_0013958 levels were associated with TNM stage ( P = 0.009) and lymphatic metastasis ( P = 0.006). The area under the receiver operating characteristic curve was 0.815 (95% confidence interval = 0.727-0.903; P < 0.001). In addition, to further illustrate the bioactivities of hsa_circ_0013958 in LAC, si RNA-mediated inhibition of hsa_circ_0013958 was performed in vitro. The results showed that hsa_circ_0013958 promoted cell proliferation and invasion and inhibited cell apoptosis in LAC. Moreover, hsa_circ_0013958 was identified as a sponge of miR-134, and thus it up-regulated oncogenic cyclin D1, which plays a pivotal role in the development of non-small cell lung cancer. In conclusion, our results suggested that hsa_circ_0013958 could be used as a potential non-invasive biomarker for the early detection and screening of LAC. [ABSTRACT FROM AUTHOR]

Purpose: High mobility group box-1 (HMGB1) is a proinflammatory, DAMP protein that participates in many pathological conditions. In this study, we evaluated the usability of CSF HMGB1 as a biomarker for the diagnosis of tuberculous meningitis (TBM). Methods: A total of 59 TBM patients and 169 control patients were included in our study. CSF samples were obtained and analyzed for HMGB1 using a commercial ELISA kit. Results: The mean CSF HMGB1 was 19.36 ng/ml in TBM patients (n = 59) versus 3.12 ng/ml in non-TB meningitis patients (n = 30), 2.13 ng/ml in patients with extra neural tuberculosis (n = 73), and 1.06 ng/m in controls (n = 66). According to the receiver operator characteristic curves, a cut-off value of 3.4 ng/ml was calculated, indicating that the sensitivity and specificity of CSF HMGB1 alone in diagnosis of TBM were 61.02 and 89.94 %, respectively. In patients with extra neural tuberculosis and a high risk of TBM, CSF HMGB1 seemed to be a good candidate for early differential diagnosis of TBM at the cut-off value of 3.8 ng/ml, when the sensitivity and specificity were 79.49 and 94.52 % respectively. Conclusion: Our finding may prove to be clinically useful, because CSF HMGB1 ELISA can be performed in almost all clinical laboratories, especially when sophisticated technologies are either time consuming or unavailable. [ABSTRACT FROM AUTHOR]

Background and Aim: MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles. Methods: In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines. Results: Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate ( P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3′-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC. Conclusion: miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC. [ABSTRACT FROM AUTHOR]

We performed a systematic review of English-language studies published during the past three decades to investigate the diagnostic performance of serum glial fibrillary acidic protein (GFAP) for the differential diagnosis of acute stroke, including intracerebral hemorrhage (ICH) and cerebral ischemia (CI). QUADAS tools were used to evaluate the quality of the study. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using fixed-effects models. Four studies met the inclusion criteria, and included 109 patients with ICH and 381 patients with CI. The summary estimates for GFAP in the ICH diagnoses had a diagnostic sensitivity of 0.80 (95% confidence interval 0.71-0.88), a specificity of 0.97 (95% confidence interval, 0.94-0.98), and a diagnostic odds ratio (DOR) of 119.55 (95% confidence interval: 51.75-276.19). The area under curve (AUC) and Q value for the sROC curves were 0.97 and 0.92, respectively. Therefore, GFAP showed high diagnostic accuracy for acute stroke differential diagnosis. [ABSTRACT FROM AUTHOR]

Digital quantitative immunohistochemical analysis of protein biomarker expression offers a broad dynamic range against which clinical outcomes may be measured. Semi-quantitative expression data represented as an H-score is produced by computer generated average intensity of positive staining given weight by the percentage of cells showing positive staining. While patient H-scores vary for biological reasons, variation may also arise from preanalytic technical issues, such as differences in fixation protocols. In this study, we present data on two candidate calibrator nuclear-localized proteins, SNRPA and SnRNP70, with robust and consistent expression levels across breast cancers. Quantitative expression measurement of these two candidate biomarkers may potentially be used to eliminate the effect of differences in preanalytic processing of specimens by normalizing H-scores derived from test biomarkers of interest. To examine the effects of preanalytical fixation variation on biomarker quantitation and potential utility of candidate calibrators to address such issues, 6 surgically-resected human breast cancer patient specimens were divided into 6 portions and fixed under distinct conditions (fixation following resection in formalin for 2 hr, 8 hr or 48 hr, or held overnight at 4°C in buffered saline prior to formalin fixation for 2 hr, 8 hr, or 48 hr). We find H-score variation between fixation conditions within individual patient's tumors that were stained for XPF, ATM, BRCA1, pMK2 and PARP1. Most interestingly, detectable expression of SNRPA and SnRNP70 is covariant to test biomarkers under distinct fixation conditions and so these hold the potential for serving as calibration standards for general antigen preservation and reactivity. [ABSTRACT FROM AUTHOR]

As key regulators of apoptosis, BAD and defender against apoptotic cell death 1 (DAD1) are associated with cancer initiation and progression. Multiple studies have demonstrated that BAD and DAD1 serve critical roles in several types of cancer and perform various functions, such as participating in cellular apoptosis, invasion and chemosensitivity, as well as their role in diagnostic/prognostic judgement, etc. Investigating the detailed mechanisms of the cancerous effects of the two proteins will contribute to enriching the options for targeted therapy, and may improve clinical treatment of cancer. The present review summarizes research advances regarding the associations of BAD and DAD1 with cancer, and a hypothesis on the feasible relationship and interaction mechanism between the two proteins is proposed. Furthermore, the present review highlights the potential of the two proteins as therapeutic targets and valuable diagnostic and prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Pituitary tumor transforming gene-1 (PTTG1) is a novel oncogene and overexpressed in a wide variety of human cancers. However, the clinical and prognostic significance of PTTG1 in non-small cell lung cancer (NSCLC) is still unknown. The expression status of PTTG1 in NSCLC at the publicly available GEO databases ( GSE19804 ) was observed. The mRNA and protein expression of PTTG1 in NSCLC tissues and cell lines was detected by qRT-PCR and Western blot, and the association between PTTG1 expression and clinicopathological factors was analyzed by immunohistochemistry. In our Results, PTTG1 was one of genes overexpressed in NCSLC samples compared with paired adjacent normal lung samples in microarray data (GSE19804). PTTG1 mRNA and protein expressions were increased in NSCLC tissues and cell lines. PTTG1 protein expression was correlated with malignant status and poor prognosis of NSCLC patients. In conclusion, PTTG1 is correlated with NSCLC progression and as an independent poor prognostic factor in NSCLC patients. [ABSTRACT FROM AUTHOR]

Crohn's disease is a recurrent, progressive, immune‐mediated inflammatory disease and merely manifests non‐specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT‐PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR‐582‐5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606–0.796, p <.001). While PBMC miR‐96‐5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p <.001) and endoscopic activity (ρ = 0.512, p =.015). Furthermore, PBMC miR‐96‐5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609–0.844, p =.001) than C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR‐582‐5p may be further utilized as a diagnostic biomarker, while miR‐96‐5p may be a novel and valuable biomarker in monitoring disease activity. [ABSTRACT FROM AUTHOR]

Objectives Circulating miRNAs have been reported to have potential in detecting various diseases. However, few studies explored differentially expressed miRNAs in plasma of patients with pulmonary embolism (PE). Our study is to identify plasma miRNAs which can serve as potential biomarkers of PE. Materials and methods Exiqon miRCURY Ready-to-Use PCR Human panel I + II V1.M was conducted to identify differently expressed miRNAs in pooled plasma samples of PE patients compared with normal controls. Expressions of identified miRNAs were assessed in 37 PE patients as well as matched normal individuals followed by validation on six Beagle dogs by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results Twelve miRNAs were identified from the screening phase. Moreover, miR-134, previously reported related with PE, and hypoxia-induced miR-210 were also submitted to the validation phase. Only miR-28-3p was found significantly elevated in the plasma of PE patients. Compared with the level of plasma miR-28-3p of the dogs before PE, the elevated miR-28-3p did not alter significantly at 1, 2, 4 and 6 h after PE. The area under the receiver operating characteristic (ROC) curve of plasma miR-28-3p was 0.792 (95% confidence interval: 0.689–0.896). KEGG pathway analysis showed that miR-28-3p might involve in PE related pathways such as inositol phosphate metabolism and phosphatidylinositol signaling system. Conclusion Our study indicated that elevated plasma miR-28-3p could be used as a non-invasive and stable biomarker in the detection of PE. Further researches on the miRNA are warranted. [ABSTRACT FROM AUTHOR]

Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is an RNA-binding protein that is required for the maturation of mRNA precursor. It was previously reported that hnRNP A2/B1 was overexpressed at the early clinical stage of lung cancer, and that hnRNP B1 protein, a splicing variant of hnRNP A2 mRNA, was elevated in lung cancer tissues. In this study, we applied the immunohistochemical method, using anti-hnRNP B1 antibody to analyze the usefulness of the hnRNP B1 antibody as a prognostic marker and also as a marker useful for early detection. A total of 206 specimens were examined. Histological examination revealed this protein to be positive in 79 (71.2%) of 111 squamous cell carcinomas and in 45 (64.3%) of 70 adenocarcinomas, respectively. This protein was also expressed in 24 (63.2%) of 38 roentgenographically occult carcinomas and in seven (63.6%) of 11 dysplastic lesions. These findings suggest the possible participation of this protein in early carcinogenesis. Furthermore, the survival curve of the squamous cell carcinoma patients with hnRNP B1 overexpresseion showed a better prognosis compared with that of the patients without hnRNP B1 expression (P=0.014), whereas in adenocarcinoma patients, there was no such a difference between them (P=0.889). These findings indicate that hnRNP B1 could be a useful marker for the early detection of bronchogenic squamous cell carcinoma and that it may be a prognostic factor in this cell type. [Copyright &y& Elsevier]

Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the malignant progression of a number of human cancers. However, the roles of SPARC in lung squamous cell carcinoma (LSCC) remain elusive. In this present study, we first detected SPARC expression and investigated the relationship between SPARC expression and the clinicopathological attributes of LSCC patients. Then we constructed SPARC-overexpression model in LSCC cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. The data demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. Moreover, a serial of phenotypic experiments indicated that SPARC overexpression substantially facilitated the growth and inhibited the apoptosis in LSCC cells and xenografts. Taken together, our results suggest that SPARC is a novel prognostic marker for LSCC prognosis and SPARC significantly promotes LSCC tumorigenesis. Targeting SPARC may provide a novel therapeutic strategy for LSCC management. [ABSTRACT FROM AUTHOR]