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Using mass spectrometry-based high-throughput proteomics, we identified a membrane protein on extracellular vesicles (EVs), 90 K, which predicts poor overall survival of patients with head and neck cancer. 90 K levels in serum EVs could serve as an independent factor for poor prognosis of patients with head and neck cancer. Pre-treatment of immune competent mice with tumor-derived EVs (TDEs) elicited an immune-suppressive microenvironment for tumor cells, which was regulated by 90 K. The immunosuppressive function of TDE-90 K depends on the presence of myeloid derived suppressor cells (MDSCs) rather than regulatory T cells. The immune regulatory role of TDEs on MDSCs depends on miR-21 which is encapsulated in TDEs. Moreover, 90 K is required for the internalization of TDE cargo though interacting with integrin-β1 and anti-siglec-9 rather than directly affecting the immune function of MDSCs. 90 K modification of γδT cell-derived EVs (γδTEVs) could increase the delivery efficiency and therapeutic effect of PD-L1 siRNA by γδTEVs. We concluded that as a secreted protein modulating cell-cell and cell-matrix interactions, 90 K can be carried by TDEs to mediate the internalization and delivery of TDEs cargo by recipient cells. This function of 90 K could be utilized to improve the efficiency of EV-based drug delivery.

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease for which there is a lack of therapeutic options. Genome-wide association studies (GWASs) have identified over 100 genetic loci associated with RA susceptibility; however, the most causal risk genes (RGs) associated with, and molecular mechanism underlying, RA remain unknown. In this study, we collected 95 RA-associated loci from multiple GWASs and detected 87 candidate high-confidence risk genes (HRGs) from these loci via integrated multiomics data (the genome-scale chromosome conformation capture data, enhancer-promoter linkage data, and gene expression data) using the Bayesian integrative risk gene selector (iRIGS). Analysis of these HRGs indicates that these genes were indeed, markedly associated with different aspects of RA. Among these, 36 and 46 HRGs have been reported to be related to RA and autoimmunity, respectively. Meanwhile, most novel HRGs were also involved in the significantly enriched RA-related biological functions and pathways. Furthermore, drug repositioning prediction of the HRGs revealed three potential targets (ERBB2, IL6ST, and MAPK1) and nine possible drugs for RA treatment, of which two IL-6 receptor antagonists (tocilizumab and sarilumab) have been approved for RA treatment and four drugs (trastuzumab, lapatinib, masoprocol, and arsenic trioxide) have been reported to have a high potential to ameliorate RA. In summary, we believe that this study provides new clues for understanding the pathogenesis of RA and is important for research regarding the mechanisms underlying RA and the development of therapeutics for this condition.

Alveolar type II (AT II) is a key structure of the distal lung epithelium and essential to maintain normal lung homeostasis. Dedifferentiation of AT II cells is significantly correlated with lung tumor progression. However, the potential molecular mechanism and clinical significance of AT II-associated genes for lung cancer has not yet been fully elucidated. In this study, we comprehensively analyzed the gene expression, prognosis value, genetic alteration, and immune cell infiltration of eight AT II-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1, and PGC) in Nonsmall Cell Lung Cancer (NSCLC). The results have shown that the expression of eight genes were remarkably reduced in cancer tissues and observably relating to clinical cancer stages. Survival analysis of the eight genes revealed that low-expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, and SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2, and SFTPD mRNA expression led to a short postprogression survival (PPS). Meanwhile, the alteration of 8 AT II-associated genes covered 273 out of 1053 NSCLC samples (26%). Additionally, the expression level of eight genes were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells. In summary, this study provided clues of the values of eight AT II-associated genes as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist the design of new immunotherapies.

Infection is one of the main causes of death in cancer patients. Accurate identification of fever caused by infection could avoid unnecessary antibiotic treatment and hospitalization. This study evaluated the diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and other commonly used inflammatory markers in suspected infected adult cancer patients with fever, for better use of antibiotics. This research retrospective analyzed the clinical data of 102 adult cancer patients with fever and compared the serum levels of commonly used inflammatory markers for different fever reasons. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed. In adult cancer patients with fever, the serum PCT, CRP, IL-6, and IL-10 levels of infected patients were significantly higher than uninfected patients (median 1.19 ng/ml vs 0.14 ng/ml, 93.11 mg/l vs 56.55 mg/l, 123.74 pg/ml vs 47.35 pg/ml, 8.74 pg/ml vs 3.22 pg/ml; Mann-Whitney p = 0.000, p = 0.009, p = 0.004, p = 0.000, respectively). The ROC area under the curve(AUC) was 0.769 (95% confidence interval (CI) 0.681-0.857; p = 0.000) for PCT, 0.664 (95% CI 0.554-0.775; p = 0.009) for CRP, 0.681(95% CI 0.576-0.785; p = 0.004) for IL-6, and 0.731(95% CI 0.627-0.834; p = 0.000) for IL-10. PCT had specificity of 96.67% and positive predictive value (PPV) of 97.6%, when the cut-off value is set as 0.69 ng/ml. The serum IL-6 and IL-10 levels also had significant differences between the infected and uninfected cancer patients with advanced disease (median 128.92 pg/ml vs 36.40 pg/ml, 8.05 pg/ml vs 2.92 pg/ml; Mann-Whitney p = 0.003, p = 0.001, respectively). For the patients with neutropenia, IL-6 and IL-10 had higher AUC of 0.811 and 0.928, respectively. With a cut-off of 9.10 pg/ml, IL-10 had the highest sensitivity 83.33% and specificity 100%. In adult cancer patients, PCT had the best performance compared to CRP, IL-6, and IL-10 in differentiating infected from uninfected causes of fever, with high specificity and PPV. IL-6 and IL-10 might be useful in cancer patients with severe bloodstream infections and advanced disease. However, for patients with neutropenia, IL-10 might be more valuable than PCT in diagnosing infection.

In this work, a core-satellite optoplasmonic particle containing a silica microsphere covered with gold nanoparticles (AuNPs) was developed through wet chemistry synthesis in aqueous phase. The electroless deposition and galvanic replacement were employed to anchor AuNPs onto silica sphere surface. The escalated as well as expanded electric field enhancement within the dielectric-metallic interface was analyzed through finite difference time domain (FDTD) simulation. The numerical models and the surface-enhancement Raman spectroscopy (SERS) measurements over blood serum both support that the equatorial plane is the preferred collecting plane for improved signal intensity and stability. The nanocomposite emerged lower relative standard deviation (RSD) in repetitive measurement compared to AuNPs. In practice, this hybrid structure was applied for lung cancer diagnosis based on serum SERS spectra analysis of the patients diagnosed with nodules. The prediction with the aid of principal component analysis (PCA) and support-vector machine (SVM) was attempted for the classification of healthy, benign and relatively malignant sample groups. The accuracy of distinguish benign samples from malignant ones reaches over 90%. These advantages make the structure a promising SERS substrate for the early screening of cancer based on the non-invasive biological samples.

Esophageal cancer is a kind of cancer with high morbidity and mortality, which is accompanied by a profound poor prognosis. A prognostic nutritional index, based on serum albumin levels and peripheral lymphocyte count, has been confirmed to be significantly associated with various cancers. This study was aimed at exploring the prognostic significance of PNI in the overall survival prognosis of patients with esophageal cancer. As a real-world study based on the big database, clinical data of 2661 patients with esophageal cancer were evaluated retrospectively, and the individuals were randomly divided into training and testing cohorts. In these two cohorts, patients are classified into a high-risk group ( PNI < 49 ) and a low-risk group ( PNI ≥ 49 ). Univariate and multivariate analyses were performed to analyze the independent risk factors for the prognosis of esophageal cancer patients by using the Cox proportional hazards regression model. In this study, whether in the training cohort or the testing cohort, according to the univariate analysis, gender, tumor size, tumor grade, T stage, N stage, M stage, TNM stage, and PNI were significantly correlated with overall survival. Furthermore, the multivariate analysis showed that gender, T stage, N stage, M stage, TNM stage, and PNI were independent prognostic risk factors for esophageal cancer. PNI can be regarded as an independent prognostic factor combined with gender, T stage, N stage, M stage, and TNM stage, and it might be a novel reliable biomarker for esophageal cancer.

Background: Lung cancer is one of the most commonly diagnosed cancer and the leading cause of cancer-related death in the world. ATⅡ（alveolar type II cells, ATⅡ ）are a key structure of the distal lung epithelium and have a secretory function that is essential to maintain normal lung homeostasis. ATⅡ cells dedifferentiate into a cell stem-like state, which can continuous differentiation, proliferation, repair and damage, and helps initiate and maintain tumor progression. However, the potential mechanistic value of ATⅡ-associated genes as a clinical biomarker and therapeutic target of NSCLC has not been fully elucidated.Methods: We used the Gene Expression Profile Interaction Analysis (GEPIA) and Oncomine database to explore the expression of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) in NSCLCpatients. Then we euse the Kaplan Meierplotter and the GEPIA website to evaluate the prognosis of survival impact of differential expression of these genes. Finally, we analyzed the correlation between eight ATⅡ-associated genes and infiltration of immune cells using the TIMER website.Results: The expression levels of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were remarkably reduced in lung cancer tissues, and also observably related to clinical cancer stages. Low mRNA expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were associated with short overall survival (OS) in NSCLS patients and the low expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2 and SFTPD mRNA expression led to a short post-progression survival (PPS). Moreover, the functions of the differentially expressed eight ATⅡ-associated genes were primarily related to lung development, regulation of epithelial to mesenchymal transition, late endosome, antibacterial humoral response. Finally, the expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC in LUAD and LUSC patients were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells.Conclusion: Our study provided strong evidence of the values of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist in the design of new immunotherapies.

Extracellular vesicles (EVs) mediate intercellular communications in the tumor microenvironment and contribute to the aggressive phenomenon of cancers. Although EVs in body fluids are supposed to be ideal biomarkers for cancer diagnosis and prognosis, it remains difficult to distinguish the tumor-derived EVs from those released by other tissues. We hypothesized that analyzing the EV-related molecules in tumor tissues would help to estimate the prognostic value of tumor-specific EVs. Here, we investigate the expression of coding genes of proteins carried by small EVs (sEVs) in primary lung adenocarcinoma. Based on the protein-protein interaction network, we identified three network modules (3-PPI-Mod) as a signature that could predict recurrence. This signature was validated in three independent datasets and demonstrated better prognostic value than signature generated from gene expression alone. Meanwhile, the high-risk subgroup assigned by the signature could benefit from adjuvant chemotherapy, although it was not beneficial in unselected patients. Two out of three modules were enriched by proteins identified in sEVs from non-small-cell lung cancer cells. Furthermore, the two modules were remarkably correlated with intratumoral hypoxia score. These results suggest that the 3-PPI-Mod signature was enriched in tumor-derived sEVs and could serve as a prognostic and predictive biomarker for lung adenocarcinoma. Keywords: exosome, NSCLC, microenvironment, gene expression, adjuvant chemotherapy

Aim: To evaluate the prognostic value of pretreatment prognostic nutritional index (PNI) in nasopharyngeal carcinoma (NPC) patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Materials & methods: We conducted a retrospective study on prognostic value of PNI in NPC patients. A new prognostic marker was explored based on risk stratification with PNI and age. Results: PNI and age were two independent prognostic factors for overall survival (OS) and progression free survival besides node stage and clinical stage. Low prognostic nutritional index and high age (LPNI–HAge) was identified as an independent prognostic factor for both OS (p

Hepatocellular carcinoma (HCC) ranks third in the cause of death due to cancer. Circular RNA circSEC24 Homolog A (circSEC24A) has been uncovered to be upregulated in liver cancer. However, the function of circSEC24A in HCC is indistinct. We analyzed the microarray datasets GSE78520 and GSE94508 to search for differentially expressed circRNAs associated with HCC. Expression of circSEC24A, microRNA (miR)-455-3p, and protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Loss-of-function experiments were conducted to validate the biological function of circSEC24A in HCC cells in vitro and in vivo. Protein levels were evaluated by western blotting and immunohistochemistry (IHC). The relationship between circSEC24A or PPM1F and miR-455-3p was verified by a dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. circSEC24A was overexpressed in HCC. circSEC24A silencing decreased xenograft tumor growth in vivo and repressed proliferation, metastasis, invasion, epithelial-to-mesenchymal transition (EMT), induced cell cycle arrest, and apoptosis of HCC cells in vitro. circSEC24A acted as a molecular sponge to sequester miR-455-3p, resulting in elevating the expression of PPM1F. miR-455-3p inhibitor reversed the suppressive impact of circSEC24A silencing on malignant behaviors of HCC cells. PPM1F overexpression offsets the inhibitory effect of miR-455-3p mimic on malignant behaviors of HCC cells. circSEC24A sponged miR-455-3p to elevate the PPM1F expression, resulting in accelerating malignant behaviors of HCC cells. The study provided a potential therapeutic target for patients with HCC.

Background It has been widely reported that the prognostic nutritional index (PNI) played a pivotal role in nutritional assessment of surgical patients and tumor prognosis. In order to improve the accuracy of evaluation in Western China, we established reference intervals (RIs) of PNI in healthy controls. Methods A retrospective cohort study on healthy ethnic Han adults (18–79 years) was conducted to explore the influences of age, gender, study centers, and instruments on PNI and to establish RIs. The data came from a healthy routine examination center database and laboratory information system (LIS) of four centers in Western China, and there were 200 persons selected randomly for verification of RIs. Results Five thousand eight hundred and thirty‐nine healthy candidates were enrolled. PNI showed a marked gender dependence, and males had significantly higher PNI than females across all ages (p, A retrospective cohort study on healthy ethnic Han adults (18–79 years) was conducted to explore the influences of age, gender, study centers, and instruments on prognostic nutritional index (PNI) and to establish reference intervals (RIs). We established reference intervals of PNI in healthy Han Chinese population in Western China, and validated successfully. Further established RIs will lead to better standardizations of PNI for clinical applications.

Background It has been widely reported that the prognostic nutritional index (PNI) played a pivotal role in nutritional assessment of surgical patients and tumor prognosis. In order to improve the accuracy of evaluation in western China, we established reference intervals (RIs) of PNI in healthy controls. Methods A retrospective cohort study on healthy ethnic Han adults (18–79 years) was conducted to explore the influences of age, gender, study centers, and instruments on PNI and to establish RIs. The data came from a healthy routine examination center database and laboratory information system (LIS) of four centers in western China, and there were 200 persons selected randomly for verification of RIs. Results 5,839 healthy candidates were enrolled. PNI showed a marked gender dependence, and males had significantly higher PNI than females across all ages (P

Background: Esophageal squamous cell cancer (ESCC) was a disease with a male predominance. Accordingly, the applicability of prognostic indicators values previously set for the general population with ESCC have not been reported for determining physical state in female. Methods: A total of 2660 patients with ESCC were pooled in this study. We analyzed clinicopathologic features and clinical prognostic predictors to determine the associations with outcome by sex. We also evaluated the relationship between total cholesterol and overall survival (OS) and further assessed the influence of total cholesterol on OS was affected by other clinicopathologic variables in female cohort. We explore the interacting with gender-specific genes and TC in ESCC by bioinformatics analysis. Findings: Compared with male, female has better overall survival (log-rank P < 0.001; HR, 0.59; 95% CI, 0.51-0.67). In addition, the results confirmed that survival outcome was significantly deteriorated in male patients with low TC level (log-rank P < 0.001; HR, 1.20; 95% CI, 1.03-1.39). Interestingly, our findings, which were based on a female population, suggested a protective role of low TC level in ESCC. In accordance with the gene expression profiles from The Cancer Genome Atlas (TCGA), differential expression genes analysis shown 20 significant differential expression genes were associated with cholesterol metabolism. Subsequently, Gene ontology (GO) analysis shown these genes were mainly enriched in cholesterol transport etc. Interpretation: In our study, we suggest patients with ESCC may benefit from targeted treatments after adjusting TC concentrations based on sex-stratified, in addition to routine cancer therapies. Funding Information: Sichuan Cancer Hospital and Institution of China. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This was a retrospective clinical study and approved by Sichuan Cancer Hospital (SCCHEC-02-2020-015).

AimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

γδ T cells are a unique lymphocyte population that have been reported to have either anti- or pro-tumoral functions in several cancer types, but the mechanisms are underinvestigated. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. Hypoxia is a common feature of solid tumors and is believed to alter tumor-derived exosomes (TEXs), which mediate the hypoxic evolution of the tumor microenvironment in return. This study sought to investigate whether TEXs mediate the anti- and pro-tumoral equilibrium of γδ T cells under different oxygen pressures in the tumor microenvironment. We show that TEXs can alter the expansion and cytotoxicity of γδ T cells in an HSP70-dependent but dendritic cell-independent manner. The stimulating effects of normoxic TEXs on γδ T-cell activity were absent from hypoxic TEXs, which enhanced the suppressive effect of myeloid-derived suppressor cells (MDSCs) on γδ T cells through a miR-21/PTEN/PD-L1 regulation axis. Finally, the therapeutic outcome benefited from combined miR-21 and PD-L1 targeting in oral squamous cell carcinoma (OSCC)-bearing immunocompetent mice. We conclude that oxygen pressure in the tumor microenvironment orchestrates an anti- and pro-tumoral γδ T-cell equilibrium by altering TEX content, which subsequently regulates MDSC function in a miR-21/PTEN/PD-L1-axis-dependent manner. Our results should prompt further investigation into integrated exosomal miRNA inhibition and immune checkpoint inhibitor therapeutic modalities for patients with OSCC.

BACKGROUND Reactivation of hepatitis B virus (HBV) is a fatal complication of chemotherapy. Occult HBV infection might be reactivated in patients undergoing chemotherapy or immunosuppression. However, the mechanism of HBV reactivation induced by chemotherapy or immunosuppression remains unclear. MATERIAL AND METHODS HepG2.2.15 cells were treated with an autophagy inducer (rapamycin), an inhibitor (3-methyladenine, 3-MA), and dexamethasone. Autophagosomes were observed by a transmission electron microscope (TEM). LC3-I, LC3-II, and P62 were analyzed by western blot. HBV replicative intermediates were detected by southern blot. HBV DNA expression was quantitated with real-time polymerase chain reaction (PCR). The level of HBV surface antigen (HBsAg) in culture medium was examined by ELISA. RESULTS In this study, we find that dexamethasone stimulates HBV replication and protein expression by inducing autophagy in HepG2.2.15 cells. In contrast, autophagy inhibitor (3-MA) abrogates HBsAg secretion stimulated by dexamethasone. CONCLUSIONS Our results suggest that dexamethasone stimulates HBV replication through autophagy. This might provide a novel insight into the mechanism of glucocorticoid-mediated HBV reactivation through autophagy, which might be a new therapeutic target.

Recently, several human genetic and genomewide association studies (GWAS) have discovered many genetic loci that are associated with the concentration of the blood lipids. To confirm the reported loci in Chinese population, we conducted a cross-section study to analyse the association of 25 reported SNPs, genotyped by the ABI SNaPshot method, with the blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in 1900 individuals by multivariate analysis. Logistic regression was applied to assess the association of the genetic loci with the risk of different types of dyslipidemia. Our study has convincingly identified that 12 of 25 studied SNPs were strongly associated with one or more blood lipid parameters (TC, LDL, HDL and TG). Among the 12 associated SNPs, 10 significantly influence the risk of one or more types of dyslipidemia. We firstly found four SNPs (rs12654264 in HMGCR; rs2479409 in PCSK9; rs16996148 in CILP2, PBX4; rs4420638 in APOE-C1-C4-C2) robustly and independently associate with four types of dyslipidemia (MHL, mixed hyperlipidemia; IHTC, isolated hypercholesterolemia; ILH, isolated low HDL-C; IHTG, isolated hypertriglyceridemia). Our results suggest that genetic susceptibility is different on the same candidate locus for the different populations. Meanwhile, most of the reported genetic variants strongly influence one or more plasma lipid levels and the risk of dyslipidemia in Chinese population.

The aim of this study was to analyze the prevalence and prognostic value of myeloid differentiation factor 88 (MYD88) L265P in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We assessed the MYD88 L265P mutation using an allele-specific semi-nested polymerase chain reaction method in 53 DLBCL patients treated with R-CHOP. The MYD88 L265P mutation was detected in 16 of 53 DLBCL (30.19%) samples from patients treated with R-CHOP. Age and location were statistically significantly associated with MYD88 L265P (P=0.025, 0.033, respectively), while treatment response and tumor recurrence were not. Univariate analysis showed that B symptoms (P=0.004) and Ki-67 (P=0.03) were significantly associated with progression-free survival (PFS), while MYD88 L265P showed no significant association with overall survival and PFS. Multivariate analysis showed that B symptoms were significantly associated with PFS. Our study suggests that the prognostic value of MYD88 L265P in DLBCL patients with R-CHOP requires further research.

Objectives To determine whether the integration platelet features in blood and platelet rich plasma can establish a model to diagnose lung cancer and colon cancer, even differentiate lung malignancy from lung benign diseases. Methods 245 individuals including 159 lung cancer and 86 normal participants were divided into the training cohort and testing cohort randomly. Then, 32 colon cancers, 37 lung cancers, and 21 benign patients were enrolled into validate cohort. The whole blood and corresponding platelet rich plasma (PRP) samples from all participants were prospectively collected, and the platelet features were determined. The features which are statistically significant at the univariate analysis in the training cohort and reported significant features were entered the diagnostic model. A receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy of the model in each cohort. Results In the training cohort, multiple platelet features were significantly different in lung cancer patients, including MPV in whole blood, MPV, and platelet count in PRP and platelet recovery rate (PRR). For the training cohort, the diagnostic model for lung cancer performed well (AUC = 0.92). The probability distribution of lung cancers and controls in testing cohort were also separated well by the diagnostic model (AUC = 0.79). The diagnostic model for colon cancer also performed well (AUC = 0.79). The model also has a potential value in differentiating the lung malignancy from the benign (AUC = 0.69). Conclusion The PRR was first raised and used in the detection of lung cancer. This study identified a diagnostic model based on PRR and other platelet features in whole blood and PRP samples with the potential to distinguish patients with lung cancer or colon cancer from healthy controls. The model could also be used to distinguish between lung cancer from the benign disease.

BACKGROUND Numerous studies have shown that the hematological components of the systemic inflammatory response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune inflammation index (SII) are efficient prognostic indicators in patients with cancers. Most of the studies did not investigate the reference intervals (RIs) of these parameters in healthy controls. METHODS A retrospective cohort study was performed on healthy ethnic Han population aged between 18 and 79 years of age by retrieving the data from a healthy routine examination center database and laboratory infor-mation system of four participating centers in western China. By following the Clinical and Laboratory Standards Institute (CLSI), RIs of each parameter was established and validated. RESULTS The analysis included 5,969 healthy subjects. We found that the individual's gender can significantly influence PLR, LMR, and SII (all p 0.05). Surprisingly, we also found that with an increase in age, the PLR, LMR, and SII tend to decrease, while NLR remained stable. PLR, LMR, and SII values were significantly higher in the young adults (18 - 64 years) than in old adults (65 - 79 years) (p < 0.001). The RIs of NLR, PLR (adults), PLR (old adults), LMR and SII were 0.88 - 4.0, 49 - 198, 42 - 187, 2.63 - 9.9, 142 x 109/L - 804 x 109/L, respectively. CONCLUSIONS Our study addresses possible variations and establishes consensus for the NLR, PLR, LMR, and SII RIs for healthy Han Chinese adults in western China. Further, established RIs can standardize clinical applications and promote the use of these indicators into the routine complete blood count report.

FOXO3, AKT1 and IGF-2R are critical members of the insulin/IGF-1 signaling pathway. Previous studies showed that polymorphisms (SNPs) in FOXO3, AKT1 and IGF-2R were associated with human longevity in Caucasian population. However, the association of these SNPs in different ethnic groups is often inconsistent. Here, we investigated the association of genetic variants in three genes with human longevity in Han Chinese population. Twelve SNPs from FOXO3, AKT1 and IGF-2R were selected and genotyped in 1202 long-lived individuals (nonagenarians and centenarians) and younger individuals. Rs9486902 of FOXO3 was found to be associated with human longevity in both genders combined in this study (allelic P = 0.002, corrected P = 0.024). The other eleven SNPs were not significantly associated with human longevity in Han Chinese population. The haplotypes TTCTT, CCTTC and CTCCT of FOXO3 as well as GGTCGG and GGTCAG of AKT1 were shown to have a significant difference between case and control (P =0.006, 2.78×10-5, 4.68×10-6, 0.003,0.005, respectively). The estimated prevalence of diabetes and prediabetes in long-lived individuals was significantly lower than in common adult populations (P = 0.001, 2.3×10-26) .Therefore, the search for longevity-associated genes provides the identification of new potential targets beneficial for the treatment of diabetes.

// Huaichao Luo 1, * , Xiaoying Quan 2, * , Xiao-Yu Song 1, * , Li Zhang 1, * , Yilin Yin 3, * , Qiao He 1 , Shaolei Cai 4 , Shi Li 1 , Jian Zeng 1 , Qing Zhang 1 , Yu Gao 1 and Sisi Yu 2 1 Department of Clinical Laboratory, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China 2 Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China 3 Department of Biology, The Northeastern University, Huntington Ave, Boston, MA, USA 4 Radiotherapy Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China * These authors have contributed equally to this work Correspondence to: Sisi Yu, email: sisi-yu@hotmail.com Huaichao Luo, email: luo1987cc@163.com Keywords: red blood cell distribution width (RDW), extranodal natural killer (NK)/T-cell lymphoma, predictor, survival, radiotherapy-based treatment Received: June 12, 2017 Accepted: August 26, 2017 Published: September 30, 2017 ABSTRACT We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher’s exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P =0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P =0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS ( P =0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL.

This study was conducted to comprehensively evaluate the potential association of SKIV2L polymorphism rs429608 with age-related macular degeneration (AMD) through a meta-analysis.We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for AMD genetic studies published before August 30, 2015. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for single-nucleotide polymorphisms (SNPs) using fixed-effect models or random effect models according to between-study heterogeneity. Publication bias analyses were conducted using Egger's test.A total of five studies from published articles were included, and a total number of 2789 AMD cases and 3451 healthy controls were tested in this meta-analysis. The results demonstrated that SKIV2L rs429608 is associated with AMD under allelic model (A vs. G; OR = 0.52, 95% CI 0.44-0.62, p0.001), heterozygous model (AG vs. GG; OR = 0.51; 95%CI, 0.38-0.68; p0.001; PThis meta-analysis showed that SKIV2L rs429608 was statistically associated with AMD and it might exert a protective effect on AMD. Further investigations are needed to validate the association and confirm the role of SKIV2L in AMD.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD-associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 × 10−4 and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 × 10−4, OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders.