Search

Temporal lobe epilepsy (TLE) often occurs in childhood and is the most common type of epilepsy. Studies have confirmed that long non-coding RNAs (lncRNAs) can affect the progression of neurological diseases. This study explored the expression level of lncRNA TUG1 in TLE children and its clinical significance and investigated its role in hippocampal neurons. 86 healthy individuals and 88 TLE children were recruited. The expressions of lncRNA TUG1 and miR-199a-3p in serum were detected by qRT-PCR. Hippocampal neurons were treated with non-Mg2+ to establish TLE cell model. MTT assay and flow cytometry assay was used to detect the effect of lncRNA TUG1 on the proliferation and apoptosis of hippocampal neurons. A dual-luciferase reporter assay was done to confirm the target relationship. The expression of lncRNA TUG1 was increased in TLE children compared with the control group. The diagnostic potential was reflected by the receiver operator characteristic (ROC) curve, with the AUC of 0.915 at the cutoff value of 1.256. Elevated levels of TUG1 were detected in TLE cell models, and TUG1 knockout could enhance cell activity and inhibit cell apoptosis. MiR-199a-3p was the target of TUG1. Clinically, the serum miR-199a-3p levels showed a negative association with TUG1. LncRNA TUG1 may be a biomarker of TLE diagnosis in children, and can regulate hippocampal neuron cell activity and apoptosis via sponging miR-199a-3p.

A recent meta-analysis found a link between the PRNCR1 rs1456315 polymorphism and cancer risk. In the current study, we further investigated the association of this polymorphism with the risk and clinical stage of colorectal cancer (CRC). A total of 416 CRC patients and 416 healthy individuals were genotyped by Sanger sequencing. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Furthermore, a pooled analysis with 872 CRC cases and 1141 controls was performed by Stata 12.0 software. In both the case-control study and the pooled analysis, there was no significant link between the rs1456315 polymorphism and CRC risk. However, there was a significant link between the rs1456315 polymorphism and the clinical stage of CRC. CRC patients carrying the rs1456315 G allele were more likely to have a high-stage tumor. Further bioinformatics analysis showed that the rs1456315 polymorphism could influence the binding of miRNA to PRNCR1. In conclusion, the findings suggest that the rs1456315 polymorphism is linked to CRC clinical stage and might be used as a biomarker to predict CRC progression.

In this paper, we discuss a response adaptive randomization method, and why it should be used in clinical trials for rare diseases compared to a randomized controlled trial with equal fixed randomi...

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental disorder initiating in the first three years of life. Early initiation of management therapies can significantly improve the health and quality of life of ASD subjects. Thus, indicating the need for suitable biomarkers for the early identification of ASD. Various biological domains were investigated in the quest for reliable biomarkers. However, most biomarkers are in the preliminary stage, and clinical validation is yet to be defined. Exosome based research gained momentum in various Central Nervous System disorders for biomarker identification. However, the utility and prospect of exosomes in ASD is still underexplored. Areas covered In the present review, we summarised the biomarker discovery current status and the future of brain-specific exosomes in understanding pathophysiology and its potential as a biomarker. The studies reviewed herein were identified via systematic search (dated: June 2021) of PubMed using variations related to autism (ASD OR autism OR Autism spectrum disorder) AND exosomes AND/OR biomarkers. Expert opinion As exosomess are highly relevant in brain disorders like ASD, direct access to brain tissue for molecular assessment is ethically impossible. Thus investigating the brain-derived exosomes would undoubtedly answer many unsolved aspects of the pathogenesis and provide reliable biomarkers.

OBJECTIVE The amino-terminal peptide of type III procollagen (PIIINP) is a byproduct of type III collagen synthesis that exhibits promise as a biomarker of fibrosis, specifically in monitoring hepatic fibrosis in methotrexate treated patients. The Advia Centaur® PIIINP assay is developed for track-based automated laboratory systems and is suitable for large volume analysis. Reference intervals in children and younger adults have been published previously. Here we measured PIIINP to determine reference ranges, specifically including elderly patients, for whom such are currently lacking. METHODS Samples were collected from subjects ranging from 20 to 98 years of age. Blood donors and clinical samples from primary care patients were used for reference interval calculation. Samples were analysed using the Advia Centaur® PIIINP assay. After exclusion of samples high in alanine transaminase (AST), aspartate transaminase (ALT), and C-reactive protein (CRP) 386 samples were used in the reference interval calculation. RESULTS AND CONCLUSION We determined the following reference interval for the Advia Centaur® PIIINP assay: the lower limit of the reference interval (2.5% percentile with 95% CI) was 4.42 (4.20-4.65) µg/L and the upper limit of the reference interval (97.5% percentile 95% CI) 16.0 (15.04-17.02) µg/L.No significant differences in mean PIIINP concentrations were found between men and women. While differing mean PIIINP concentrations were seen among subjects in different age groups, the differences were small and partitioning of reference range was determined not to be necessary.

Background Most human diseases are accompanied by systems changes. Systems biomarkers should reflect such changes. The phosphorylation and dephosphorylation of biomolecules maintain human homeostasis. However, the systems biomarker characteristics of circulating alkaline phosphatase, a routine blood test conducted for many human diseases, have never been investigated. Method This study retrieved the circulating alkaline phosphatase (ALP) activities from patients with 48 clinically confirmed diseases and healthy individuals from the database of our hospital during the past five years. A detailed analysis of the statistical characteristics of ALP was conducted, including quantiles, receiving operator curve (ROC), and principal component analysis. Results Among the 48 diseases, 45 had increased, and three had decreased median levels of ALP activities compared to the healthy control. Preeclampsia, hepatic encephalopathy, pancreatic cancer, and liver cancer had the highest median values, whereas nephrotic syndrome, lupus erythematosus, and nephritis had decreased median values compared to the healthy control. Further, area under curve (AUC) values were ranged between 0.61-0.87 for 19 diseases, and the ALP activities were the best systems biomarker for preeclampsia (AUC 0.87), hepatic encephalopathy (AUC 0.87), liver cancer (AUC 0.81), and pancreatic cancer (AUC 0.81). Conclusions Alkaline phosphatase was a decent systems biomarker for 19 different types of human diseases. Understanding the molecular mechanisms of over-up-and-down-regulation of ALP activities might be the key to understanding the whole-body systems' reactions during specific disease progression.

PURPOSE: The potential for malicious use of radiation, or radiation accidents could potentially lead to acute, high radiation doses to the public. Following acute accidental exposure to high doses of radiation, medical intervention is pivotal to the survivability of the patient, and the sooner the appropriate measures are taken the better the odds for survival. Early estimates of acute accidental radiation doses can be determined via biomarkers such as dicentric chromosome analysis or scenario reconstruction using computer software. However, both take valuable time and can be expensive. Increased frequencies of abnormal neutrophils in peripheral blood, referred to as pseudo Pelger-Huët anomalies (PPHAs), have been shown to be potential biomarkers of radiation exposure in several scenarios, including the 1958 Y-12 criticality accident and the radium dial painters. PPHAs are potentially a faster and cheaper quantitative biomarker for radiation exposure, and here they were evaluated in acutely exposed rhesus macaques. METHODS AND MATERIALS: Peripheral blood smears from acutely exposed rhesus macaques were evaluated for the percentage of neutrophils that displayed the PPHA morphology using light microscopy. Irradiated animals received 0 to 8.5 Gy total body radiation using one of two strategies: (1) linear accelerator-produced 6 MV photons delivered at 80 cGy/minute; or (2) Cobalt 60-produced gamma irradiation delivered at 60 cGy/min. Zero dose animals were used to determine a baseline percentage of PPHAs, and blood smears taken periodically throughout the lifetime of exposed animals post-irradiation were used to determine the persistence and biokinetics of PPHAs. RESULTS: The baseline prevalence of the PPHA in rhesus macaques was determined to be 0.58 ± 0.46%. The dose-response curve with doses ranging from 0 Gy to 8.5 Gy (LD90/30) displayed a strong positive correlation between PPHA percentage and acute radiation dose (R(2) of 0.88 p = 3.62 × 10(−22)). Statistically significant differences were found when animals were separated into dose cohorts of 0, 4, 6.4–6.5, and 8–8.5 Gy. The biokinetics model utilized only 4 Gy exposures and blood smears taken periodically over 3.1 years post-irradiation. PPHA morphology increases quickly following irradiation and appears stable over 3.1 years post-irradiation. CONCLUSION: PPHA morphology was confirmed to be present in rhesus macaques, a dose-response relationship was constructed, and it is stable over 3 years post-irradiation. This study demonstrates that PPHA analysis can be a fast and cheap method of biodosimetry. Future studies will work to determine the accuracy of dose determination and lower limits of detection.

Understanding factors associated with disease severity and mortality from coronavirus disease (COVID-19) was critical for effective risk stratification. We aimed to investigate the association between biomarkers of clinical laboratory tests, including serum C-reactive protein (CRP), serum amyloid protein (SAA), lactate dehydrogenase (LDH), and D-dimer (DD) and poor prognosis of COVID-19. We have searched many studies on COVID-19 on PubMed (Medline), Web of Science and Cochrane until 1 March 2021. The interest of this study was original articles reporting on laboratory testing projects and outcome of patients with COVID-19 that comprises mortality, acute respiratory distress syndrome (ARDS), need for care in an intensive care unit (ICU), and severe COVID-19. After synthesizing all data, we performed meta-analysis of random effects, and determined mean difference (MD) and standard mean difference at the biomarker level for different disease severity. A total of 7,739 patients with COVID-19 were pooled from 32 studies. CRP was significantly associated with poor prognosis of COVID-19 (SMD = 0.98, 95% CI = (0.85, 1.11), p < .001). Elevated SAA was associated with an increased composite poor outcome in COVID-19 (SMD = 1.06, 95% CI = (0.39, 1.72), p = .002). An elevated LDH was associated with a composite poor outcome (SMD = 1.18, 95% CI = (1.00, 1.36), p < .001). Patients with a composite poor outcome had a higher DD level (SMD = 0.91, 95% CI = (0.79, 1.02), p < .001). This meta-analysis showed that elevated serum CRP, SAA, LDH, and DD were associated with a poor outcome in COVID-19.

Angiogenesis is in a constant balance between pro and anti-angiogenic factors. Neoangiogenesis, implicated in metastatic spreading is characterized in solid cancers, but fairly new in chronic lymphocytic leukemia (CLL). We hypothesize that secretion of angiogenic factors could be correlated to the pathogenesis of CLL, and therefore predict the outcome of patients. We investigated concentrations of 22 cytokines and chemokines in 137 non-del 17p B-CLL patients, treated with a fludarabine-cyclophosphamide-rituximab (FCR)-based regimen. We constructed a biomarker index defining different risk groups based on lymphocyte count, the intensity of CD20 antigen on CD19+ cells, Ang-2, and PDGF-BB plasma concentrations at diagnosis. Four groups were defined, exhibiting specific molecular signatures and correlated with progression-free survival of patients. Our results suggest that we can determine at diagnosis of non-del 17p B-CLL patients, those with a very high probability of progression-free survival, independently of IGVH mutational status and residual disease at the end of treatment.

Paired-like homeobox 2B (PHOX2B) is a highly sensitive and specific biomarker for diagnosing neuroblastoma, as well as detecting minimal residual disease in neuroblastoma. The clinical significance...

Objectives. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Design. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm (n = 23); TAPSE 18-24 mm (n = 55); TAPSE ≤17 mm (n = 13); permitting the detailed statistical analysis of derived data. Results. Serum levels of gal-3 in all patients correlated with age (r = 0.36. p

Ribonucleotide Reductase (RNR) is a two-subunit (RRM1, RRM2) enzyme, responsible for the conversion of ribonucleotides to deoxyribonucleotides required for DNA replication. To evaluate RNR as a biomarker of response to 5-azacytidine, we measured RNR mRNA levels by a quantitative real-time PCR in bone marrow samples of 98 patients with myelodysplastic syndrome (MDS) treated with 5-azacytidine with parallel quantification of the gene promoter's methylation. Patients with low RRM1 levels had a high RRM1 methylation status (p = 0.005) and a better response to treatment with 5-azacytidine (p = 0.019). A next-generation sequencing for genes of interest in MDS was also carried out in a subset of 61 samples. Splicing factor mutations were correlated with lower RRM1 mRNA levels (p = 0.044). Our results suggest that the expression of RNR is correlated with clinical outcomes, thus its expression could be used as a prognostic factor for response to 5-azacytidine and a possible therapeutic target in MDS.

Despite research advances, recently identified biological markers for depression are either non-specific or impractical in daily clinical practice. Hence, we aim to identify a novel biomarker: δEPCD, the electrophysiologic coefficient of depressiveness. δEPCD must be sensitive and specific to the vulnerability towards depression. It should also detect the presence of a depressive clinical state and be able to quantify its severity. Moreover, it should be easily accessible and cost-effective. Accordingly, combining high-frequency heart rate variability (HF-HRV), which reflects a reduction in vagal tone, and tryptophan metabolism, which influences serotonin synthesis pathway, may have a good diagnostic and prognostic accuracy in depression. δEPCD is the multiplication of the intrinsic difference between state 0 (rest) and state 1 (exposure to stress) of HF-HRV and the plasma concentration ratio between quinolinic acid and kynurenine. δEPCD theoretically fluctuates between -1000 and 0 where being closer to 0 signifies no vulnerability to depression. Individuals with a score between -16.7 and -167 have a high vulnerability to depression. Finally, individuals with a δEPCD closer to -1000 have the most severe forms of depression. δEPCD is theoretically conceived to be easy to assess and monitor which makes it a candidate for further evaluation of reliability and validity.CLINICAL SIGNIFICANCEDepression is currently diagnosed based on emotional and behavioural symptoms; however there is currently a rising interest in the field of neurobiological markers that could improve diagnostic accuracy.Many current biological approaches are primarily based on single neurobiological markers that are either non-specific or impractical in daily clinical practice.Among other neurological effects, depression may modify the parasympathetic nervous system tone and disturb the tryptophan metabolism.The electrophysiological coefficient of depressiveness δEPCD combines heart rate variability (HRV) and tryptophan metabolism to reflect the intrinsic individual vulnerability towards depression and the inherent severity of an index depressive disorder.δEPCD is the intrinsic difference between state 0 (without stress) and state 1 (exposed to a stressful task) of the high-frequency heart rate variability multiplied by the intrinsic difference between both states, e.g. state 0 and 1, of the plasma concentration ratio of quinolinic acid over kynurenine.

In the present study, we investigated the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and overall survival, toxicity and treatment response for North Indian adenocarcinoma patients. The polymorphisms of MTHFR gene in north Indian adenocarcinoma patients were assessed by PCR-RFLP. Our data observed that patients with mutant genotype (C/C) for 1298 A>C) polymorphism showed higher trend of median survival time compared to patients bearing the wild type genotype (A/A) (MST= 13.93 vs. 7.97, p=0.12). Further, we observed patients with the heterozygous genotype for A1298C polymorphism had 12-fold risk of diarrhea (AOR =12.54, 95% CI = 1.54-101.86, p=0.018). The patients with heterozygous genotype (CT) of the C677T polymorphism had 5.34-fold increased risk of developing neutropenia (AOR=5.34, 95% CI=1.49-19.06, p=0.009). Our results suggest that MTHFR polymorphisms are associated with hematological toxicity. MTHFR polymorphism might impact the development of pemetrexed and platinum-related toxicities but not as a clinical predictor of efficiency.

Objective: p75 neurotrophin receptor (p75NTR) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75NTR(p75ECD) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75ECD levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p = 0.008). Increased urinary p75ECD levels were inversely associated with ALSFRS-R in ALS patients (r = -0.32, 95% CI [-0.43, -0.21], p < 0.001). Conclusions: Given the associations between p75ECD and ALS found in this meta-analysis, urinary p75ECD levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.

Yifan Zhu,1,&ast; Lisheng Wang,1,&ast; Yanying Nong,2 Yunxiao Liang,3 Zongsheng Huang,3 Pingchuan Zhu,4 Qisong Zhang1 1Medical College of Guangxi University, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China; 2Department of Gastroenterology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, People’s Republic of China; 3Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qisong ZhangMedical College of Guangxi University, Guangxi University, No. 100, East Daxue Road, Nanning, Guangxi, 530004, People’s Republic of ChinaTel +86 0771-3387105Email zhangqisong@gxu.edu.cnBackground: As a key precancerous lesion, colorectal advanced adenoma (CAA) is closely related to the occurrence and development of colorectal cancer (CRC). Effective identification of CAA-related biomarkers can prevent CRC morbidity and mortality. Lipids, as an important endogenous substance, have been proved to be involved in the occurrence and development of CRC. Lipidomics is an advanced technique that studies lipid metabolism and biomarkers of diseases. However, there are no lipidomics studies based on large serum samples to explore diagnostic biomarkers for CAA.Methods: An integrated serum lipid profile from 50 normal (NR) and 46 CAA subjects was performed using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Lipidomic data were acquired for negative and positive ionization modes, respectively. Differential lipids were selected by univariate and multivariate statistics analyses. A receiver operator characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of differential lipids.Results: A total of 53 differential lipids were obtained by combining univariate and multivariate statistical analyses (P < 0.05 and VIP > 1). In addition, 12 differential lipids showed good diagnostic performance (AUC > 0.90) for the discrimination of NR and CAA by receiver operating characteristic curve (ROC) analysis. Of them, the performance of PC 44:5 and PC 35:6e presented the outstanding performance (AUC = 1.00, (95% CI, 1.00– 1.00)). Moreover, triglyceride (TAG) had the highest proportion (37.74%) as the major dysregulated lipids in the CAA.Conclusion: This is the first study that profiled serum lipidomics and explored lipid biomarkers with good diagnostic ability of CAA to contribute to the early prevention of CRC. Twelve differential lipids that effectively discriminate between NR and CAA serve as the potential diagnostic markers of CAA. An obvious perturbation of TAG metabolism could be involved in the CAA formation.Keywords: colorectal advanced adenoma, biomarker, serum lipidomics, UHPLC-HRMS, colorectal cancer

Nan Lu,1,&ast; Jinhui Liu,2,&ast; Mengting Xu,2,&ast; Jianqiang Liang,2 Yichun Wang,3 Zhipeng Wu,4 Yan Xing,2 Feiyang Diao1 1Department of Reproduction, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 4Department of Urology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiyang DiaoDepartment of Reproduction, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaEmail phenix_y@163.comYan XingDepartment of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of ChinaEmail 13951891712@163.comBackground: Globally, ovarian cancer (OC), the deadliest gynecologic malignancy, remains a major cause of mortality, with a rising number of cases in many low- and middle-income countries. Immunotherapy has been proven to be promising for OC. There is increasing awareness of the vital role that tumor mutation burden (TMB) plays in predicting the efficacy of immunotherapy. Women with a family history of OC are at higher risk of the disease due to gene mutations. However, whether these gene mutations are related to immune response and TMB remains to be explored.Methods: Our present work analyzed genetic mutation data of OC patients obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, and we identified 11 frequently mutated genes, namely, APOB, CSMD3, DST, FAT3, FLG, HMCN1, MUC16, RYR1, TP53, TTN, and USH2A, in accordance with the overlap of two databases.Results: A statistically higher TMB was detected by whole-exome sequencing in patients with OC with CSMD3 mutation than in those with mutations in the other frequently mutated genes. Prognosis analysis performed with patients from the TCGA cohort revealed that those with CSMD3 mutation had an overall survival (OS) that was inferior to that of those with wild-type CSMD3. Gene set enrichment analysis (GSEA) and CIBERSORT analysis indicated that OC samples with CSMD3 mutations had significant involvement of pathways related to the immune response.Conclusion: In summary, we found that CSMD3 mutation is highly correlated with increased TMB and poor clinical prognosis and that it might function as a biomarker for predicting prognosis and choosing an immunotherapy regimen.Keywords: ovarian cancer, CSMD3, tumor mutation burden, prognosis, tumor-infiltrating immune cells

Jianwei Wang,1,2,&ast; Lili Yu,1,3,&ast; Yulong Sun,4,&ast; Liangming Zhang,1,3 Mingshu Tu,1,3 Liqing Cai,1,3 Xiaoqing Yin,3,5 Xiaojie Pan,1,6 Tao Wang,4 Yi Huang1,3,7,8 1Provincial Clinical College, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, Fuzhou, 350008, People’s Republic of China; 3Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 4Shanghai Liangrun Biomedicine Technology Limited Company, Shanghai, 200000, People’s Republic of China; 5Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China; 6Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 7Central Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 8Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Huang; Tao Wang Email hyi8070@126.com; wangtao@microdiag.comPurpose: Our pilot study has shown that cystatin SN (CST1) protein is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. We intend to develop a chemiluminescent enzyme immunoassay (CLEIA) available for serum CST1 detection and define the diagnostic value of CST1 detection for early ESCC patients, and establish a panel of CST1 with traditional tumor markers to improve the diagnostic sensitivity for early ESCC.Methods: Detection performance of CLEIA for CST1 was evaluated by linearity, detection limit, accuracy, precision, anti-interference and stability. Diagnostic performance of CST1 for early ESCC was evaluated by detecting CST1 of 112 early ESCC, 107 esophageal benign lesions (EBL), and 151 healthy controls (HC). CEA, CYFRA21-1 and SCC-Ag were detected by chemiluminescence immunoassay (CLIA).Results: The linear range and detection limit of CLEIA for CST1 were 6.25– 400 pg/mL and 1.35 pg/mL, respectively; the average recovery rate was 102.65%; CVs of intra-batch precision and inter-batch precision were < 1/4 TEa and < 1/3 TEa, respectively; 8 interferents including 7 common interferents and CST4 had no interference on CST1 detection; stability evaluation showed good sample and reagent stability. The level and positive rate of CST1 in early ESCC group were significantly higher than those in EBL/HC groups (P< 0.05). The diagnostic sensitivity of CST1 for early ESCC was 31.25% (specificity 92.64%, AUC 0.654). The diagnostic sensitivity of traditional tumor markers ranged from 16.07% to 28.57%, at > 93.0% specificity, and SCC-Ag showed the highest AUC (0.709). Combination of CST1 and CEA, SCC-Ag exhibited the highest AUC up to 0.736 (sensitivity 49.11%, specificity 89.53%).Conclusion: CLEIA has excellent detection performance for CST1. CST1 might be a prospective serological biomarker for early diagnosis of ESCC, while combination of CST1 and CEA, SCC-Ag might improve the early diagnostic performance.Keywords: esophageal squamous cell carcinoma, cystatin SN, chemiluminescence enzyme immunoassay, methodological evaluation, early diagnosis

Jianting Du,1,2 Jiekun Qian,1,2 Bin Zheng,1,2 Guobing Xu,1,2 Hao Chen,1,2 Chun Chen1,2 1Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Chun ChenDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350000, People’s Republic of ChinaTel +86 13805069983Fax +86 591-87113828Email dujt1220@fjmu.edu.cnBackground: Lung cancer (LUCA) is one of the most prevalent human malignancies, and the leading cause of cancer-related deaths worldwide. Previous reports have shown that miR-21-5p plays a vital role in development of various tumors. Here, we explored the relationship between miR-21-5p/PIK3R1 axis and prognosis of patients with lung adenocarcinoma (LUAD).Methods: MiRNAseq data, deposited in The Cancer Genome Atlas (TCGA) database, was downloaded and used to determine patterns of miR-21-5p expression in both LUAD and normal lung tissues. Statistical analyses and data visualization were performed using dbDEMC v3.0 platform, starBase v3.0 database and packages implemented in R software. Next, we employed TargetScan Human, miRDB and DIANA Tools databases to predict miR-21-5p target genes, then analyzed their expression patterns as well as prognostic value in LUAD.Findings: Most human cancers overexpressed miR-21-5p. Specifically, miR-21-5p was significantly upregulated in LUAD tissues relative to normal lung tissues (P < 0.001), and this high expression was significantly correlated with poor patient prognosis (hazard ratio [HR]=1.45, P = 0.014). PIK3R1 was predicted as a miR-21-5p target gene, and both were negatively correlated (r=− 0.218, P < 0.01). Notably, PIK3R1 was significantly downregulated in LUAD, relative to normal lung tissues (P < 0.01), with its overexpression significantly associated with poor prognosis of LUAD patients (HR = 0.62, P = 0.0014).Conclusion: miR-21-5p is a potential prognostic biomarker for LUAD patients. Moreover, it might be playing a role in LUAD progression by regulating PIK3R1 expression.Keywords: lung adenocarcinoma, miR-21-5p, PIK3R1, survival

Yuan-Jie Liu,1– 3,&ast; Sheng-Yan Yin,2,3,&ast; Shu-Hong Zeng,2,3 Yi-Dou Hu,1 Meng-Qi Wang,2,3 Pan Huang,1 Jie-Pin Li1– 3 1Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 2Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 3No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie-Pin Li; Pan HuangDepartment of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Chang ‘an South Road No. 77, Zhangjiagang, Jiangsu, 215600, People’s Republic of ChinaTel +8615150224526; +8613921976647Email zjgzy027@njucm.edu.cn; yezipan2020@126.comPurpose: The identification of biomarkers and effective therapeutic targets for gastric cancer (GC), the most common cause of cancer-related deaths around the world, is currently a major focus in research. Here, we examined the utility of LHFPL6 as a prognostic biomarker and therapeutic target for GC.Methods: We explored the clinical relevance, function, and molecular role of LHFPL6 in GC using the MethSurv, cBioPortal, TIMER, Gene Expression Profiling Interactive Analysis, ONCOMINE, MEXPRESS, and EWAS Atlas databases. The GSE118919, GSE29272, and GSE13861 datasets were used for differential expression analysis. Using The Cancer Genome Atlas, we developed a Cox regression model and assessed the clinical significance of LHFPLs. In addition, we used the “CIBERSORT” algorithm to make reliable immune infiltration estimations. Western blot and immunohistochemistry were used to examine protein expression. Cell migration and invasion were assessed using transwell experiments. THP-1-derived macrophages and GC cells were co-cultured in order to model tumor–macrophage interactions in vitro. The levels of CD206 and CD163 were measured using immunofluorescence assays. The results were visualized with the “ggplot2” and “circlize” packages.Results: Our results showed that in GC, LHFPL6 overexpression was significantly associated with a poor prognosis. Our findings also suggested that LHFPL6 may be involved in the activation of the epithelial–mesenchymal transition. Furthermore, LHFPL6 expression showed a positive correlation with the abundance of M2 macrophages, which are potent immunosuppressors.Conclusion: LHFPL6 could be a prognostic biomarker and therapeutic target for GC.Keywords: gastric cancer, LHFPL6, biomarker, EMT, M2 macrophages

Jie Cheng,1,&ast; Siyang Wang,2,&ast; Jingying Jia,3 Qian Chen,3 Yunxiao Song,4 Junsheng Li1 1Department of Urinary Surgery, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Department of Geratology, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 3Department of Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 4Department of Clinical Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junsheng LiDepartment of Urinary Surgery, Shanghai Xuhui Central Hospital, No. 966 Huaihai Road, Shanghai, 200031, People’s Republic of ChinaTel +86-21 31270810Email lijunshengdy@163.comPurpose: Red cell distribution width (RDW), an inflammation biomarker, has been linked to poor outcomes in patients with different types of cancers. The present study aimed to investigate the relationship between pre-/post-treatment 3-month RDW levels and changes in RDW with 3-year prognosis of prostate cancer.Patients and Methods: A total of 348 patients with prostate cancer were recruited between June 1, 2012 and June 1, 2017 and were followed up for at least 3 years. RDW was measured with the Mindray BC-6800Plus automatic blood counting system at pre- and post-treatment 3-month. Demographic and clinical information of the participants were also collected. The overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan–Meier method. Cox regression and competing risk regression analyses were performed.Results: During the follow-up period, 51 (14.66%) deaths occurred. The levels of pre- and post-treatment RDW levels were significantly higher in the death group than in the survival group (p< 0.001). In the death group, the level of RDW continued to rise in most subjects, and the mean level of RDW was significantly higher at post-treatment than pre-treatment, contrary to the results observed in the survival group. Multivariate Cox regression analysis revealed that high pre-treatment RDW, high post-treatment RDW, and persistently higher RDW were independently associated with OS and CSS (p< 0.001). Similar results were observed in the competing risk regression analysis. Kaplan–Meier analysis revealed that patients with higher pre-treatment RDW levels, higher post-treatment RDW levels, and persistently higher RDW levels had poorer 3-year OS and CSS rates (p< 0.05).Conclusion: The levels of and changes in RDW before and after treatment were associated with the 3-year prognosis of prostate cancer, suggesting that RDW might be an efficient prognostic predictor in patients with prostate cancer.Keywords: red cell distribution width, prostate cancer, prognostic, overall survival, cohort study

Shaochong Lin,1,2 Junpeng Du,3 Jun Hao,1 Xiaohua Luo,1 Han Wu,1 Huifang Zhang,1 Xinxin Zhao,1 Lida Xu,1 BaoJin Wang1,2 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Henan International Joint Laboratory of Ovarian Malignant Tumor, Zhengzhou, 450052, People’s Republic of China; 3Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: BaoJin WangDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Kangfu Front Street, Erqi District, Zhengzhou, 450052, People’s Republic of ChinaTel +86 156 3927 7692Fax +86 371-66903480Email 2995269936@qq.comPurpose: Family with sequence similarity 83 (FAM83) is a newly discovered oncogene family, and the members of which can affect the prognosis of patients with malignant tumors via various mechanisms. However, the functions and molecular mechanisms of FAM83 genes in ovarian cancer (OC) have not yet been investigated. This study aimed to explore the clinical significance and prognostic value of FAM83 genes in OC.Materials and Methods: We used a series of bioinformatics databases (Oncomine, GEPIA, cBioPortal, Kaplan–Meier plotter, DAVID and TIMER) to investigate the expression status, prognostic value, genetic alteration and biological function of all eight FAM83 genes in OC. In addition, a tissue microarray cohort (TMA) comprising 99 ovarian tumor tissues and 19 normal ovarian tissues was used to validate the protein expression and clinicopathological significance of FAM83H.Results: Several datasets demonstrated the mRNA levels of FAM83A/D/E/F/H were significantly higher in OC compared with that in normal tissue. Moreover, the upregulation of FAM83D/H has been mutually confirmed in the Oncomine and GEPIA datasets. Kaplan–Meier survival analysis indicated that the FAM83D/H upregulation could predict poor prognosis of OC patients who had shorter overall survival (OS) and progression-free survival (PFS). In addition, cBioportal analysis indicated that the genetic alterations of FAM83 genes might affect the survival outcomes of patients with OC. Furthermore, KEGG analysis suggested that FAM83D/H are involved in the progression of OC through the cell cycle signaling pathway, and they had significant co-expression relationship with cell cycle-related genes. Finally, immunohistochemistry analysis confirmed the high expression of FAM83H protein in OC tissue, suggesting that its expression is positively correlated with the FIGO stage and pathological subtype of OC.Conclusion: This study elucidated the expression status and prognostic value of FAM83 genes in OC and identified that FAM83D/H might be potential targets for the prognostic monitoring and targeted therapy of OC.Keywords: FAM83s, ovarian cancer, prognosis, immunohistochemistry, biomarker

Joanna Kami&nacute;ska,1 Violetta Dymicka-Piekarska,1 Robert Chrzanowski,2 Karol Sawicki,2 Anna J Milewska,3 Justyna Zi&nacute;czuk,1 Marzena Tylicka,4 Marek Jadeszko,2 Zenon Mariak,2 Ewa M Kratz,5 Joanna Matowicka-Karna,1 Johannes Kornhuber,6 Piotr Lewczuk,6,7 Olga M Koper-Lenkiewicz1 1Department of Clinical Laboratory Diagnostics, Medical University of Bia&lstrok;ystok, Bia&lstrok;ystok, 15-269, Poland; 2Department of Neurosurgery, Clinical Hospital of the Medical University of Bia&lstrok;ystok, Bia&lstrok;ystok, 15-276, Poland; 3Department of Statistics and Medical Informatics, Medical University of Bia&lstrok;ystok, Bia&lstrok;ystok, 15-295, Poland; 4Department of Biophysics, Medical University of Bia&lstrok;ystok, Bia&lstrok;ystok, 15-089, Poland; 5Department of Laboratory Diagnostics, Division of Laboratory Diagnostics, Faculty of Pharmacy, Wroc&lstrok;aw Medical University, Wroc&lstrok;aw, 50-556, Poland; 6Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, 91054, Germany; 7Department of Neurodegeneration Diagnostics, Medical University of Bia&lstrok;ystok, Bia&lstrok;ystok, 15-269, PolandCorrespondence: Joanna Kami&nacute;ska; Olga M Koper-LenkiewiczDepartment of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., Bia&lstrok;ystok, 15-269, PolandTel/Fax +48 85 7468584Email joanna.kaminska@umb.edu.pl; o.koper@wp.plBackground: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth.Methods: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers’ instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6.Results: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p< 0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p< 0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227).Conclusion: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.Keywords: cerebrospinal fluid, CSF, interleukin 6, IL-6, unruptured intracranial aneurysm, UIA, IL-6 Quotient

Lei Xue,1,&ast; Jinyuan Liu,1,&ast; Jiaheng Xie,2,&ast; Jinhua Luo1 1Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhua LuoDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaEmail luojinhua2021@163.comJiaheng XieDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaEmail xiejiaheng@njmu.edu.cnBackground: Currently, lung adenocarcinoma is the most common form of lung cancer. Although the pathogenesis of lung adenocarcinoma is progressing rapidly, the mortality rate of lung adenocarcinoma is still high. Therefore, it is necessary to search for a new biomarker to guide the prognosis of lung adenocarcinoma.Methods: The significance of SLC16A3 in lung adenocarcinoma was investigated by multi-database analysis. GEPIA, UALCAN, TIMER, Cbioportal, and R software were used for research.Results: Our study found that SLC16A3 was highly expressed in lung adenocarcinoma and was associated with poor prognosis. Further studies have shown that SLC16A3 is involved in some metabolic pathways. Not only that, SLC16A3 is associated with immune cell infiltration and tumor mutation burden (TMB).Conclusion: SLC16A3 has good prognostic significance in lung adenocarcinoma, based on which to explore treatment options may improve the prognosis of patients.Keywords: lung adenocarcinoma, transporter, SLC, glucose metabolism, immunotherapy

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD). However, prior studies have typically utilized small and poorly characterized samples, and they have not analyzed the subtests of the RBANS. The current study sought to expand on prior work by examining the relationship between the Indexes and subtest scores of the RBANS and three AD biomarkers: amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and APOE ε4 status.One-hundred twenty-one older adults across the AD continuum (intact, amnestic Mild Cognitive Impairment, mild AD), who were mostly Caucasian and well-educated, underwent assessment with the RBANS and collection of the three biomarkers.Greater amyloid deposition was significantly related to lower scores on all five Indexes and the Total Scale score of the RBANS, as well as 11 of 12 subtests. For bilateral hippocampal volume, significant correlations were observed for 4 of the 5 Indexes, Total Scale score, and 9 of 12 subtests, with smaller hippocampi being related to lower RBANS scores. Participants with at least one APOE ε4 allele had significantly lower scores on 3 of the 5 Indexes, Total Scale score, and 8 of the 12 subtests.In this sample of participants across the dementia spectrum, most RBANS Indexes and subtests showed relationships with the amyloid deposition, hippocampal volumes, and APOE status, with poorer performance on the RBANS being associated with biomarker positivity. Although memory scores on the RBANS have traditionally been linked to biomarkers in AD, other Index and subtest scores also hold promise as indicators of AD. Replication in a more diverse sample is needed.

Objectives: To investigate the correlation between sleep disorders and the concentrations of three metals analyzed from hair samples of PD patients.The hypothesis of an involvement of an imbalance of metals in the development of Parkinson's Disease (PD) has been strengthened by several clinical chemistry studies. Interestingly, while sparse, some studies have correlated the imbalance of metals in PD patients with comorbidities present in this disease. Although not all PD sufferers present sleep disturbances, significant disorders of sleep are common in this population. Methods: Sleep evaluation was divided into three parameters: sleep quality, excessive daytime sleepiness and clinically probable REM Sleep Behavior Disorder. Flame atomic absorption spectrometry (F AAS) was used to assess the concentrations of calcium, iron and zinc in hair samples collected from a population of PD patients registered in a Brazilian city and from controls (a total of 53 subjects). All subjects lived within a restricted geographical region and were exposed to similar environmental conditions. Results: PD patients with poor sleep quality and excessive daytime sleepiness exhibited significant differences in concentrations of calcium, but not iron or zinc when compared to levels found in controls and PD patients who do not report these sleeping problems. Discussion: Our data suggest that different subgroups of PD patients exist, and clinical chemistry could be useful as a biomarker for these subgroups, which needs to be confirmed in a larger patient population. Further, our data raise the question regarding whether normalization of calcium levels could improve the sleep quality and somnolence in PD patients.

Minimal residual disease (MRD) detection is an important prognostic parameter in patients with refractory or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). CD79a has been reported to exhibit a high degree of linage-specificity for B-cell differentiation, with a specificity of 88% and a sensitivity of 100%. In this study, we investigated the efficiency and prognostic role of cytoplasmic CD79a (cCD79a) antibody-gated multicolor flow cytometry (MFC) in MRD detection in patients with B-ALL who received CD19-targeted chimeric antigen receptor (CAR) T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The retrospective analysis was carried on to 59 patients who accepted allo-HSCT after CD19-CAR-T infusion from June 2016 to May 2017. The MFC MRD statuses before and after allo-HSCT were both strongly correlated with the transplantation prognosis, the MFC panel with cCD79a gating can effectively monitor MRD after CD19 CAR T-cell therapy and predict the prognosis after allo-HSCT. Trial registration: ClinicalTrials#: ChiCTR-IIh-16008711.gov: NCT03173417. Registered 30 May 2017 - retrospectively registered, https://www.clinicaltrials.gov/.

Long noncoding RNAs (lncRNAs) have been found to be correlated with different cell biological processes and progression of various types of cancers including colorectal cancer (CRC). CRC is one of the most widespread cancers, thus, introducing new methods or biomarkers for its early diagnosis are desirable. The Crucial role of RMRP lncRNA and its nearby gene, CCDC107, has been shown in numerous types of malignancies. The current study aims to compare expression of CCDC107 and RMRP in CRC and its adjacent normal tissues. For this study, RT-qPCR was applied to evaluate the expression level of candidate gene and lncRNA in 72 CRC cases. ROC curve was plotted to examine the diagnostic capacity. Additionally, for more supporting data, The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal server and GEPIA online database were enrolled to investigate the effect of both genes expression level on clinicopathological parameters. We observed expression of CCDC107 was significantly down-regulated in the patients group (p < 0.05) which was associated with poor disease-free survival, friction genome alteration and surgical margin status. In contrast, RMRP expression was not significantly altered in CRC versus normal tissues. ROC curve analysis revealed that the area under the curve (AUC) for CCDC107 and RMRP were 0.871 and 0.5, respectively. Additionally, expression of these two genes did not change significantly in different stages of the disease. In conclusion, CCDC107 significantly decreased in colorectal tumor samples and can be considered as a biomarker for diagnostic aims in CRC, but not RMRP.

Introduction Multiple Sclerosis (MS) is a chronic autoimmune and neurodegenerative disease of the central nervous system with a course dependent on early treatment response. Increasing evidence also suggests that despite eliminating disease activity (relapses and lesions), many patients continue to accrue disability, highlighting the need for a more comprehensive definition of treatment success. Optimizing disability outcome measures, as well as continuously improving our understanding of neuroinflammatory and neurodegenerative biomarkers is required. Areas covered This review describes the challenges inherent in classifying and monitoring disease phenotype in MS. The review also provides an assessment of clinical, radiological, and blood biomarker tools for current and future practice. Expert opinion Emerging MRI techniques and standardized patient outcome assessments will increase the accuracy of initial diagnosis and understanding of disease progression.

OBJECTIVE To explore the relationship between circular RNA (circRNA) in gestational diabetes mellitus (GDM) and the metabolic profile at the molecular level, and find a biological marker that can predict GDM early. METHODS A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between January 10 2018 and February 20 2019. Reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of hsa_circRNA_102682 in serum and analyze its correlation with lipid metabolism parameters. RESULTS Advanced age and higher pre-pregnancy body mass index (BMI) during pregnancy are risk factors for GDM. The expression level of hsa_circ_102682 was lower among the cases than the controls (p=.000). The levels of triglyceride, apolipoprotein A1 (APOA1), APOB, and high-density lipoprotein cholesterol (HDL-C) were different between the controls and cases (p

Blood eosinophils have been proposed as a surrogate biomarker of airway eosinophilia that can be used for treatment decisions in patients with COPD, mainly for the identification of candidates for the initiation or withdrawal of therapy with inhaled corticosteroids, as well as for the identification of patients at future risk of exacerbations. In this manuscript we review the recent literature on blood eosinophils in the management of patients with COPD, in an attempt to answer the major questions that are relevant for the practicing clinician. A growing body of evidence suggests that eosinophilic COPD may constitute a separate phenotype of the disease with distinct clinical features and blood eosinophils may represent a potential candidate surrogate marker for specific COPD patients. Several points still need to be clarified, including the role of eosinophils for the identification of candidates for future COPD therapies, yet blood eosinophils plausibly represent the most dependable and promising biomarker for the precision management of COPD today.

Major cause of mortality in ovarian cancer can be attributed to a lack of specific and sensitive biomarkers for diagnosis and prognosis of the disease. Uncovering the mutations in genes involved in crucial oncogenic pathways is a key step in discovery and development of novel biomarkers. Whole exome sequencing (WES) is a powerful method for the detection of cancer driver mutations. The present work focuses on identifying functionally damaging mutations in patients with high-grade serous ovarian carcinoma (HGSC) through computational analysis of WES. In this study, WES data of HGSC patients was retrieved from the genomic literature available in sequence read archive, the variants were identified and comprehensive structural and functional analysis was performed. Interestingly, I66T and V138I mutations were found to be co-occurring in the IL7R gene in four out of five HGSC patient samples investigated in this study. The V138I mutation was located in the fibronectin type-3 domain and computationally assessed to be causing disruptive effects on the structure and dynamics of IL7R protein. This mutation was found to be co-occurring with the neutral I66T mutation in the same domain which compensated the disruptive effects of V138I variant. These comprehensive studies point to a hitherto unexplored significant role of the IL7R gene in ovarian carcinoma. It is envisaged that the work will lay the foundation for the development of a novel biomarker with potential application in molecular profiling and in estimation of the disease prognosis.Communicated by Ramaswamy H. Sarma.

AIM To analyze the structural features and therapeutic response in clinical and subclinical inflammatory choroidal neovascularization (i-CNV) detected inside subretinal hyperreflective material (SHRM) using swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). METHODS In this prospective interventional study, subjects with quiescent posterior uveitis presenting with SHRM on SS-OCT and CNV network on SS-OCTA were included. Subjects with intraretinal fluid/subretinal fluid (IRF/SRF) received intravitreal antivascular endothelial growth factor (anti-VEGF) injections, while those with no IRF/SRF either received treatment or observation for 6 months until they developed IRF/SRF or decrease in best-corrected visual acuity (BCVA)/metamorphopsia. Serial comparisons included SHRM width and height and intrinsic flow signal on OCTA. RESULTS 28 eyes of 22 subjects (12 males; mean age: 29.52 ± 12.56 years) were evaluated. Subjects with IRF/SRF at baseline (n = 6 eyes; termed as exudative iCNVs) receiving treatment showed significant improvement in BCVA (p = .017), SHRM width/height and flow signal (p

Introduction : Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third cancer-related cause of death worldwide. In recent years, several systemic therapy drugs including sorafenib, lenvatinib, regorafenib, cabozantinib ramucicurab, nivilumab, and pembrolizumab have been approved by FDA for advanced HCC. However, their insufficient efficacy, toxicity, and drug resistance require clinically applicable and validated predictive biomarkers. Areas covered : Our review covers the recent advancements in the identification of proteomic/genomic/epigenomic/transcriptomic biomarkers for predicting HCC treatment efficacy with the use of multi-kinase inhibitors (MKIs), CDK4/6 inhibitors, and immune checkpoint inhibitors (ICIs). Alpha-fetoprotein, des-carboxyprothrombin, vascular endothelial growth factor, angiopoietin-2, and dysregulated MTOR, VEGFR2, c-KIT, RAF1, PDGFRβ have the potential of proteomic/genomic biomarkers for sorafenib treatment. Alanine aminotransferase, aspartate aminotransferase, and albumin-bilirubin grade can predict the efficacy of other MKIs. Rb, p16, and Ki-67, and genes involved in cell cycle regulation, CDK1-4, CCND1, CDKN1A, and CDKN2A have been proposed for CD4/6 inhibitors, while dysregulated TERT, CTNNB1, TP53 FGF19, and TP53 are found to be predictors for ICI efficacy. Expert opinion : There are still limited clinically applicable and validated predictive biomarkers to identify HCC patients who benefit from systemic therapy. Further prospective biomarker validation studies for HCC personalized systemic therapy are required.

Although serum ferritin (SF) has been shown in several studies to be a potential cancer biomarker, the results are inconsistent. Herein, a systematic review was performed to investigate the clinical SF levels in different types of tumors in order to verify the role of SF levels as a biomarker for cancer diagnosis. The search was performed using the PubMed/Medline, Cochrane Library, and Scopus databases. Observational studies comparing SF levels between healthy adults and patients with cancer were included. The meta-analysis was carried out according to the inverse variance and random effects model. The standardized mean differences (SMDs) were assessed at 95% confidence intervals (CIs). We found that SF was higher in patients with cancer (SMD 3.07; CI 1.96,4.17), especially for head and neck cancer (SMD 3.88; CI 0.42,7.34), lung cancer (SMD 1.72; CI 0.67,2.78), pancreatic cancer (SMD 6.79; CI 5.66,7.91), and renal cell carcinoma (SMD 1.77; CI 0.48,3.05). Moreover, in the advanced stages (Stages III and IV), ferritin levels were higher than in healthy adults (SMD 4.89; CI 2.72,7.06, and SMD 8.40; CI 6.99,9.82, respectively). SF acts as a biomarker for pancreatic cancer, renal cell carcinoma, lung cancer, and head and neck cancer and is a sensitive biomarker for the detection of advanced stages of tumors.

The epithelial cells of the mammary gland secrete extracellular nanovesicles known as exosomes that carry and protect microRNAs and other various signaling biomolecules. Milk exosomes are stable du...

OBJECTIVE: The prevalence of pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been estimated from an ethnically and sociodemographically diverse community-based random sample of 10,119 youth aged 5-17. A team of physicians made a final diagnosis of ME/CFS if the participants met criteria for up to three selected case definitions following medical and psychiatric evaluations. We assessed whether a salivary biomarker of fatigue could identify youth with ME/CFS. STUDY DESIGN: We examined the ratio of the concentrations of 2 peptide fragments in saliva, referred to as the Fatigue Biomarker Index (FBI), in participants from our study diagnosed with ME/CFS (n=59) and matched controls (n=39). RESULTS: Significant overall differences were found in the FBI between those participants with severe ME/CFS and those with ME/CFS and the controls. CONCLUSIONS: If confirmed in other populations, the FBI could serve as an objective test to aid in the diagnosis of severe ME/CFS.

Liang Chen,1,&ast; Yunhua Lin,2,&ast; Guoqing Liu,2 Rubin Xu,1 Yiming Hu,3 Jiaheng Xie,4 Hongzhu Yu1 1Department of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People’s Republic of China; 2The First Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu, People’s Republic of China; 4Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhu YuFuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaTel +86 177 5686 0568Email hongzhu.620929@aliyun.comJiaheng XieDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86 177 5686 0568Email xiejiaheng@njmu.edu.cnObjective: Hepatocellular Carcinoma (HCC) has the characteristics of high incidence and poor prognosis. However, the underlying mechanism of HCC has not yet been fully elucidated. This study aims to investigate the potential mechanism and clinical significance of signal sequence receptor (SSR1) in HCC through bioinformatics methods.Methods: Four online (GEPIA, TIMER, TCGA, and GEO) databases were used to explore the expression level of SSR1 in HCC. The summary receiver operating characteristic (SROC) analysis and standardized mean difference (SMD) calculation were performed further to detect its diagnostic ability and expression level. The Human Protein Atlas (HPA) database was applied to verify the level of SSR1 protein expression. Chi-square test and Fisher’s exact test were carried out to determine the clinical relevance of SSR1 expression. KM survival analysis, univariate and multivariate COX regression analyses were employed to explore the prognostic impact of SSR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were implemented to reveal the underlying mechanism of SSR1. Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR) was used to verify the expression of SSR1 in HCC.Results: SSR1 was significantly overexpressed in HCC (SMD=1.25, P=0.03) and had the moderate diagnostic ability (AUC=0.84). SSR1 expression was significantly correlated with T stage, Gender, Pathologic stage (All P< 0.05). Patients with high SSR1 expression had shorter overall survival (OS). Univariate and multivariate Cox regression analyses showed that high SSR1 expression was an independent risk factor for poor prognosis. KEGG analysis showed that SSR1-related genes were enriched in the cell cycle, DNA replication, and TGF-beta signaling pathway. GSEA analysis also shows that the high expression of SSR1 is related to the activation of the above three signal pathways. qRT-PCR showed that the SSR1 expression in HCC was significantly higher than the Peri-carcinoma tissue (PHCC) and the corresponding normal liver tissue.Conclusion: SSR1 expression was significantly up-regulated, and it had the potential as a biomarker for the diagnosis and prognosis of HCC. It was very likely to participate in the occurrence and development of HCC by regulating the cell cycle. In summary, our study comprehensively analyzed the clinical value of SSR1 and also conducted a preliminary study on its potential mechanism, which will provide inspiration for the in-depth study of SSR1 in HCC.Keywords: hepatocellular carcinoma, signal sequence receptor, SSR1, prognosis, diagnostic

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system, accounting for approximately 10–15% of kidney cancers in the world. Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with the highest mortality. Surgical resection or puncture of tumor tissue is still an important clinical treatment and diagnosis of ccRCC, but its high recurrence rate and poor prognosis often lead to the short survival period of patients. Hence, the development of novel molecular biomarkers is of great clinical importance. miRNAs are endogenous non-coding small RNAs with a length of 19–24 nt. A growing number of studies have reported that miRNAs, as proto-oncogenes or tumor suppressor genes, play a key role in the development of ccRCC and might be effective diagnostic and prognostic biomarkers. In addition, miRNAs can also predict the efficacy of treatment drug, thus improving the accuracy of clinical medication. Furthermore, non-invasive detection of miRNAs or extracellular vesicles (EV) in body fluids has better convenience and repeatability, which shows remarkable advantages compared with tissue detection. In this review, we summarized the typical miRNAs reported in recent years and place emphasis on evaluating miRNAs in different body fluids to provide reference for the clinical diagnosis and prognosis of ccRCC in the future.

Lingli Chen,1,&ast; Jianfeng Hong,2,&ast; Renjing Hu,3,&ast; Xiaomei Yu,1 Xindong Chen,1 Shaoxiong Zheng,1 Yuan Qin,1 Xiumei Zhou,1 Yigang Wang,1 Liping Zheng,2 Hongming Fang,2 Pengfei Liu,4 Biao Huang1 1Department of Immunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China; 2Department of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 3Department of Laboratory, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Gastroenterology, The Jiangyin Clinical College of Xuzhou Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao HuangImmunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571-86843187Email jswxhb@163.comHongming FangDepartment of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571 83865858Email 3295988078@qq.comPurpose: The present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis.Patients and Methods: The double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed.Results: Serum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL).Conclusion: sTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.Keywords: T cell immunoglobulin and mucin domain molecule 3, time-resolved fluorescence immunoassay, biomarker, gastric cancer

Sihui Wen,&ast; Shenghao Cheng,&ast; Shaobing Xie, Hua Zhang, Zhihai Xie, Weihong Jiang Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihai Xie; Weihong JiangDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People’s Republic of ChinaEmail xiedoctor@csu.edu.cn; jiangwh68@126.comBackground: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence.Methods: We recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence.Results: The serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence.Conclusion: Our data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.Keywords: YKL-40, chronic rhinosinusitis with nasal polyps, endotypes, recurrence

Sisi Chang,1 Yahui Zhu,2 Yutan Xi,2 Fuyan Gao,2 Juanjuan Lu,2 Liang Dong,1 Chunzheng Ma,1 Honglin Li1 1Department of Oncology, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of China; 2Department of Oncology, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Chunzheng Ma; Honglin LiHenan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of ChinaTel +86-18801611544Email mchzh666@126.com; 46991701@qq.comPurpose: To evaluate the role of DSCC1 in LUAD.Patients and Methods: Based on TCGA and GTEx, the Wilcoxon rank-sum test was used to compare the expression differences of DSCC1 between the normal samples of GTEx combined TCGA and the unpaired tumor samples of TCGA, and to compare DSCC1 expression values between tumor tissues and paired normal LUAD tissues in the TCGA cohort. Kruskal–Wallis rank-sum test, Wilcoxon rank-sum test, and logistics regression were used to compare the relationship between the expression of DSCC1 and the clinicopathological parameters. The biological function of DSCC1 was annotated by GSEA and ssGSEA, while Kaplan–Meier and Cox regression analysis were used to evaluate the prognostic value of DSCC1. Furthermore, the time-dependent ROC curve was used to analyze the diagnostic efficacy of DSCC1 in LUAD.Results: We downloaded the RNA-Seq data of 513 LUAD cases. The expression of DSCC1 was significantly correlated with T stage (OR = 1.04(1.02– 1.07), P = 0.002), pathological stage (OR=1.03 (1.01– 1.05), P = 0.008) and TP53 status (OR=1.10 (1.07– 1.14), P < 0.001). The high expression of DSCC1 was significantly correlated with DSS (HR=1.56 (1.07– 2.26), P = 0.021) and OS (HR=1.53 (1.14– 2.05), P = 0.004). Moreover, ROC curve analysis (AUC=0.845, CI (0.820-0.870)) indicated DSCC1 as a potential diagnostic molecule for LUAD. In the group with high DSCC1 expression phenotype, down-regulation of EGFR signal, reduction of IL-6 deprivation, cell cycle, and p53 signal pathway were significantly abundant. Spearman correlation analysis showed that the expression of DSCC1 was positively correlated with the infiltration of Th2 cells, T Helper cells.Conclusion: Our results suggest that DSCC1 may be an important biomarker for the treatment of LUAD.Keywords: DSCC1, LUAD, GSEA, prognosis, biomarker

Objective: Hyaluronan, a glycosaminoglycan that forms a major constituent of the extracellular matrix, has been shown to be increased in the serum of patients with amyotrophic lateral sclerosis (ALS) with longer disease duration. We sought to determine whether measures of venous hyaluronan may serve as a predictive marker for disease progression in patients with ALS. Methods: Sixty-two patients with ALS, and 59 healthy control participants provided a plasma sample for the assessment of hyaluronan. Hyaluronan was compared against functional measures of disability, disease progression, and survival. Results: Hyaluronan was lower in patients with ALS when compared to healthy controls. Plasma hyaluronan was positively correlated with the change in the revised ALS functional rating scale, ΔFRS. Hyaluronan was also found to improve the prognostic power of the ΔFRS. Conclusion: Hyaluronan may serve as a predictive marker for functional decline in patients with ALS. Longitudinal studies are needed to fully explore the prognostic value of hyaluronan as a biomarker for disease progression, and to improve our understanding of components of the extracellular matrix specific to the pathophysiology of ALS.

The purpose of the current study was to examine the ability of psychosocial constructs and biomarker measures of overtraining and stress to predict athlete burnout, as mediated by training distress...

The identification of Ultra-High Risk (UHR) individuals is thought to be useful for early intervention to improve psychosis outcomes. However, transition rates vary widely, and there is an effort to make these criteria more specific and accurate. Neuroinflammation has been discussed in the pathophysiology of psychosis. The metabolism of eicosanoids is a key process in inflammatory states. Therefore, we investigated whether the study of the inflammatory COX-2 pathway through the quantification of the eicosanoid levels can be a useful approach for the characterisation of UHR individuals.One hundred and twenty-two individuals were included in this study (67 UHR and 55 controls) based on performance on the Prodromal Questionnaire. UHR status was assessed by Structured Interview for Prodromal Syndromes (SIPS). We determined the levels of Prostaglandin FConcentrations of PGEOur findings suggest that overactivation of the COX-2 pathway may be related to an increased risk for psychosis. However, our data do not allow us to draw conclusions related to the cause-effect mechanisms. Future studies should determine whether the levels of the eicosanoids have a predictive value for the transition of UHR to frank psychosis.

In this study, the effects of enrofloxacin-based antibiotic (EBA) used as a drug in veterinary medicine were evaluated on zebrafish embryos and larvae. The embryos were exposed to 17.56–300 mg L−1 ...

Shifei Yao,1,2 Nanning Luo,1,2 Jiaoyang Liu,1,2 He Zha,1 Yuanhang Ai,1,2 Juan Luo,1,2 Shi Shi,3 Kaifeng Wu1,2 1Department of Laboratory Medicine, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of China; 2Scientific Research Center, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of China; 3Department of Laboratory Medicine, The Fourth People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of ChinaCorrespondence: Kaifeng WuDepartment of Laboratory Medicine/Scientific Research Center, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of ChinaTel +86 85123116548Email kiphoonwu@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined.Methods: We did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis.Results: At baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6– 119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8– 55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1– 1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4– 689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P= 0.008) and inversely with sICAM-1 (r= − 0.609, P= 0.021) and aspartate aminotransferase levels (r= − 0.560, P= 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment.Conclusion: The present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.Keywords: COVID-19, PGRN, soluble adhesion molecules, pathogenesis, biomarker

Background The red blood cell distribution width (RDW)–albumin ratio (RA) is a new biomarker, which is d-efined as RDW divided by albumin. This study aimed at determining the prognostic values of RA for diabetic ketoacidosis (DKA). Methods Data were obtained from Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III) and the RA calculated. Multivariate Cox regression analysis was performed to determine the correlation between RA and 90-day mortality or 365-day mortality. To further investigate the association with RA and mortality, the patients were divided into two groups. The second outcome was the association between the incidence of DKA-related infections and RA. Results For DKA patients in the ICU, RA was significantly correlated with 90-day mortality (HR: 2.1, 95% CI: 1.5, 3.0, p

Jie Min,1 Fei Dong,1 Pin Wu,2 Xiaopei Xu,1 Yimin Wu,2 Yanbin Tan,1 Fan Yang,1 Ying Chai2 1Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang Province, People’s Republic of China; 2Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang Province, People’s Republic of ChinaCorrespondence: Ying ChaiDepartment of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People’s Republic of ChinaTel +86-57187783642Fax +86 571-87068001Email chaiy@zju.edu.cnPurpose: Immunotherapy has made breakthroughs in the treatment of non-small-cell lung cancer (NSCLC); however, only a subset of patients achieved long-term survival, so it is of great importance to find a biomarker of lung cancer thus guide immunotherapy. Studies have shown that the infiltration level of tissue resident memory CD8+ T cells (CD8+ TRMs) is positively correlated with lung cancer prognosis and can be an ideal biomarker for assessing the tumor local immune status. We screened the radiomic features associated with CD8+ TRMs as targets in NSCLC surgical specimens by radiomic approaches, and established a radiomic predictive model to assess the local immune status, which may provide a scientific reference for lung cancer treatment strategies.Patients and Methods: We retrospectively analyzed the NSCLC surgical specimens immune cell database and extracted CD8+ TRMs cell data, preoperative CT scan data were achieved. A total of 97 patients containing complete preoperative data were included, radiomic features were extracted from the preoperative CT image data. All the patients were divided into two groups, namely high-CD8+ TRMs infiltrated group and low-CD8+ TRMs infiltrated group, based on the proportion of CD8+ TRMs cells subset in the immune cell population. The most valuable radiomic features and semantic features were extracted and selected, and a neural network model was established to predict the level of CD8+ TRMs cell infiltration level to assess the tumor local immune status.Results: The NSCLC tumor immune status predictive model was built to discriminate high- from low-CD8+ TRMs with an area under the curve (AUC) of 0.788 (95% CI) in the training set and 0.753 (95% CI) in the validation set.Conclusion: The radiomic models using CT image data showed a good predictive performance for accessing NSCLC immune status thus has great potential for personalized therapeutic decision making.Keywords: non-small-cell lung cancer, NSCLC, radiomic, tumor immune status, tissue resident memory CD8+ T cells, CD8+ TRMs

Xiangui Meng,1– 3,&ast; Hongwei Yuan,1– 3,&ast; Weiquan Li,1– 3,&ast; Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaTel +86-18602752025Fax +86 2785776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Studies report that conventional treatment of clear cell renal cell carcinoma (ccRCC) is effective, but several advanced patients present with poor prognosis. The current study explored potential new tumor markers and therapeutic targets in advanced ccRCC.Methods: Biomarker gene expression of ccRCC was retrieved from GEO database and the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database. Gene ontology (GO) analysis and protein–protein interaction (PPI) networks of biomarker genes were constructed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Kaplan–Meier analysis and receiver operating characteristic curve (ROC) analysis were performed to explore the prognostic and diagnostic roles of these genes. Gene set enrichment analysis (GSEA) analysis was used to determine hallmark functions of the biomarker genes. qRT-PCR was used to verify the reliability of the analysis results in tumor tissues.Results: A total of 21 upregulated genes were identified between advanced ccRCC and early ccRCC (grade III+IV vs grade I+II). Gene ontology analysis showed that the 21 upregulated genes were mainly implicated in biological processes including metabolic and lipid transport. The findings showed that 7 out of the 21 genes were significantly upregulated in 72-paired samples retrieved from the TCGA-KIRC. High expression of 5 genes indicated a poor prognosis of overall survival and disease-free survival in KIRC. Three genes effectively distinguished renal cancer tissue and adjacent renal tissues in a total of 533 ccRCC samples. GSEA showed that the 3 biomarkers were significantly enriched in epithelial–mesenchymal transition, G2M checkpoint, and angiogenesis. The results of qRT-PCR showed that STEAP3, IBSP, and AQP9 had a significant identification effect in ccRCC.Conclusion: The findings showed that 3 biomarkers were significantly upregulated in advanced ccRCC and could be used for diagnosis, prediction, and potential novel therapeutic targets for progression of ccRCC.Keywords: advanced ccRCC, biomarker, progression, differentially expressed genes