Expression of CD4+CD25+CD127Low regulatory T cells and cytokines in peripheral blood of patients with primary liver carcinoma.

Objective: To assess the clinical utility of the ratio of CD4+CD25+CD127low regulatory T cells (Tregs) in subjects at high risk of HCC, investigate the relationship between the percentage of Tregs and the expression of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 in patients with hepatocellular carcinoma before and after treatment. Methods: Peripheral venous blood was collected from patients with liver cancer before and after treatment. The proportion of CD4+CD25+CD127low Tregs was detected by flow cytometry. The levels of TGF-ß1 and IL-10 in serum were detected by enzyme-linked immunosorbent assay, and were compared with healthy subjects as a control group. Results: The proportion of CD4+CD25+CD127low to CD4+T lymphocytes in patients with hepatocellular carcinoma was significantly higher than that in healthy controls (P<0.01). The proportion of CD4+CD25+CD127lowTregs, whose AUC of ROC curve was 0.917, could effectively separate the HCC patients from the healthy subjects with a diagnostic sensitivity of 90%, specificity of 80%. The proportion of CD4+CD25+CD127low to CD4+T lymphocytes and the levels of TGF-ß1 and IL-10 in patients with hepatocellular carcinoma after the operation and chemotherapy were significantly lower than those before treatment (P<0.05).The proportion of CD4+CD25+CD127lowTregs was positively correlated with the concentrations of TGF-ß1 and IL-10 before and after treatment of primary liver cancer (P<0.05). Conclusion: CD4+CD25+CD127lowTregs may be a significant predictor of HCC biopsy outcome and play an inhibitory role on effector T cells by regulating cytokines.

Circulating tumor cells: a valuable marker of poor prognosis for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the prognostic value of circulating tumor cells (CTCs) in nasopharyngeal carcinoma (NPC). METHODS: Cox's proportional hazards regression models were used to identify whether CTCs was a poor prognostic factor for NPC. Chi-square tests were used to analyze and compare the distribution characteristics of CTCs in NPC. ROC curve was used to estimate the cut-off point of CTCs. Kaplan-Meier survival analyses were used to observe the prognostic value of CTCs alone and in combined with Epstein-Barr Virus DNA (EBV-DNA). RESULTS: CTCs was confirmed to be an independent risk factor for poor prognosis of NPC by Cox's regression models that enrolled 370 NPC cases and took age, gender, EBV-DNA and CTCs as variables. The proportion of CTCs in stage IV NPC was statistically different from that in stage III; the cut-off point of CTCs between stage IV (288 cases) and stage III (70 cases) NPC estimated by ROC curve was 0.5. The prognosis of advanced NPC patients became worse with the increase of CTCs count. The combined detection of CTCs and EBV-DNA could better predict the prognosis of NPC compared with the single detection of EBV-DNA.

Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

BACKGROUND: This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. METHODS: The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. RESULTS: Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P < 0.01], and the decision curve analyses showed that the nomogram model had a higher overall net benefit than did the TNM stage. Based on the total prognostic scores (TPS) of the nomogram, we further subdivided the study cohort into three groups: low risk (TPS ≤ 13.5), intermediate risk (13.5 < TPS ≤ 20.0) and high risk (TPS > 20.0). CONCLUSION: The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

Grass carp which survive Dactylogyrus ctenopharyngodonid infection also gain partial immunity against Ichthyophthirius multifiliis.

Dactylogyrus ctenopharyngodonid and Ichthyophthirius multifiliis are 2 important ectoparasites of fish. Both parasites can induce an immune response in fish that leads to a decrease in parasitic infection intensity and the development of resistance against parasitic reinfection. The present study evaluated whether grass carp Ctenopharyngodon idella that survived a D. ctenopharyngodonid infection could develop immunity against infection by D. ctenopharyngodonid and I. multifiliis. The results demonstrated that when grass carp were infected with D. ctenopharyngodonid, the number of red blood cells and the percentages of thrombocytes, monocytes, and neutrophils in the white blood cells increased significantly in the early stage of infection. The percentage of lymphocytes increased over time following parasitic infection. The mean infection intensity of D. ctenopharyngodonid decreased to 0 on Day 28. The activities of serum acid phosphatase, alkaline phosphatase, lysozyme, and superoxide dismutase increased significantly after D. ctenopharyngodonid infection. In addition, the grass carp that survived a previous D. ctenopharyngodonid infection could completely resist D. ctenopharyngodonid reinfection and partially resist I. multifiliis infection.

Elevated Preoperative Serum Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) Ratio Is Associated with Better Prognosis in Patients Undergoing Curative Treatment for Gastric Adenocarcinoma.

The level of anine aminotransferase/aspartate aminotransferase (ALT/AST) ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR) was associated with prognosis for gastric adenocarcinoma (GA) has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS). Survival analysis was conducted with the Kaplan-Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of <0.05 was considered to be statistically significant. A total of 231 patients were finally enrolled. The median overall survival was 47 months. Multivariate analysis indicated that preoperative LSR was an independent prognostic factor in GA. Patients with LSR ≤ 0.80 had a greater risk of death than those with LSR > 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388-0.958; p = 0.032), along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044-4.756; p < 0.001) and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119-3.422; p = 0.019). Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions.

A Novel Inflammation-Based Stage (I Stage) Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma.

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222-3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177-3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.

Influence of Preoperative Serum Aspartate Aminotransferase (AST) Level on the Prognosis of Patients with Non-Small Cell Lung Cancer.

The purpose of this work is to analyze preoperative serum aspartate aminotransferase (AST) levels and their effect on the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical operation. These analyses were performed retrospectively in patients with NSCLC followed by surgery; participants were recruited between January 2004 and January 2008. All clinical information and laboratory results were collected from medical records. We explored the association between preoperative serum AST and recurrence-free survival (RFS), and the overall survival (OS) of NSCLC patients. Kaplan-Meier analysis and Cox multivariate analysis, stratified by the AST median value, were used to evaluate the prognostic effect. A chi-squared test was performed to compare clinical characteristics in different subgroups. A p-value of ≤0.05 was considered to be statistically significant. A total of 231 patients were enrolled. The median RFS and OS were 22 and 59 months, respectively. The AST levels were divided into two groups, using a cut-off value of 19 U/L: High AST (>19 U/L), n = 113 vs. low AST (≤19 U/L), n = 118. Multivariate analysis indicated that preoperative serum AST > 19 U/L (hazard ratio (HR) = 0.685, 95% confidence interval (CI): 0.493-0.994, p = 0.046 for RFS, HR = 0.646, 95% CI: 0.438-0.954, p = 0.028 for OS) was an independent prognostic factor for both RFS and OS. High preoperative serum AST levels may serve as a valuable marker to predict the prognosis of NSCLC after operation.

Discovery and Correction of Spurious Low Platelet Counts due to EDTA-Dependent Pseudothrombocytopenia.

BACKGROUND: Ethylene diamine tetraacetic acid dependent pseudothrombocytopenia (EDTA-PTCP) is a laboratory artifact that may lead to unnecessary evaluation and treatment of patients. The purpose of this article is to discuss how to identify EDTA-PTCP and correct spurious low platelet counts in clinical laboratories. METHODS: We use two criteria to screen for platelet aggregation: (1) an abnormal platelet count in EDTA-treated blood from a patient lacking clinical signs of a platelet disorder, and (2) an instrument flag for platelet clumps. EDTA-PTCP was confirmed by microscopic examination for platelet agglutination and by platelet counts that corrected with citrate sample. In addition, the time course of EDTA-PTCP was investigated in samples from 26 patients anticoagulated with EDTA-K2 and sodium citrate. Amikacin (5 mg/ml) was added to tubes with EDTA-K2 or sodium citrate from seven additional cases in order to confirm its dissociative effect on platelet aggregation. RESULTS: In our laboratory, the overall incidence of EDTA-PTCP was approximately 0.09%; and the duration was between 2 weeks and 6 months. EDTA-PTCP was time-dependent and occurred as early as 10 min after sample collection. Weaker agglutination could also occur in most corresponding citrate-treated samples. The dissociative effect of amikacin on platelet agglutination was case-specific and not concentration-dependent. CONCLUSIONS: The method of screening for platelet clumping with the help of XE5000 images is convenient. The decline in the platelet count is related to the length of time and the intensity of chelation. Amikacin supplement is not always effective for correcting platelet counts in vitro.

Highly sensitive detection platform-based diagnosis of oesophageal squamous cell carcinoma in China: a multicentre, case-control, diagnostic study.

BACKGROUND: Early detection and screening of oesophageal squamous cell carcinoma rely on upper gastrointestinal endoscopy, which is not feasible for population-wide implementation. Tumour marker-based blood tests offer a potential alternative. However, the sensitivity of current clinical protein detection technologies is inadequate for identifying low-abundance circulating tumour biomarkers, leading to poor discrimination between individuals with and without cancer. We aimed to develop a highly sensitive blood test tool to improve detection of oesophageal squamous cell carcinoma. METHODS: We designed a detection platform named SENSORS and validated its effectiveness by comparing its performance in detecting the selected serological biomarkers MMP13 and SCC against ELISA and electrochemiluminescence immunoassay (ECLIA). We then developed a SENSORS-based oesophageal squamous cell carcinoma adjunct diagnostic system (with potential applications in screening and triage under clinical supervision) to classify individuals with oesophageal squamous cell carcinoma and healthy controls in a retrospective study including participants (cohort I) from Sun Yat-sen University Cancer Center (SYSUCC; Guangzhou, China), Henan Cancer Hospital (HNCH; Zhengzhou, China), and Cancer Hospital of Shantou University Medical College (CHSUMC; Shantou, China). The inclusion criteria were age 18 years or older, pathologically confirmed primary oesophageal squamous cell carcinoma, and no cancer treatments before serum sample collection. Participants without oesophageal-related diseases were recruited from the health examination department as the control group. The SENSORS-based diagnostic system is based on a multivariable logistic regression model that uses the detection values of SENSORS as the input and outputs a risk score for the predicted likelihood of oesophageal squamous cell carcinoma. We further evaluated the clinical utility of the system in an independent prospective multicentre study with different participants selected from the same three institutions. Patients with newly diagnosed oesophageal-related diseases without previous cancer treatment were enrolled. The inclusion criteria for healthy controls were no obvious abnormalities in routine blood and tumour marker tests, no oesophageal-associated diseases, and no history of cancer. Finally, we assessed whether classification could be improved by integrating machine-learning algorithms with the system, which combined baseline clinical characteristics, epidemiological risk factors, and serological tumour marker concentrations. Retrospective SYSUCC cohort I (randomly assigned [7:3] to a training set and an internal validation set) and three prospective validation sets (SYSUCC cohort II [internal validation], HNCH cohort II [external validation], and CHSUMC cohort II [external validation]) were used in this step. Six machine-learning algorithms were compared (the least absolute shrinkage and selector operator regression, ridge regression, random forest, logistic regression, support vector machine, and neural network), and the best-performing algorithm was chosen as the final prediction model. Performance of SENSORS and the SENSORS-based diagnostic system was primarily assessed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). FINDINGS: Between Oct 1, 2017, and April 30, 2020, 1051 participants were included in the retrospective study. In the prospective diagnostic study, 924 participants were included from April 2, 2022, to Feb 2, 2023. Compared with ELISA (108·90 pg/mL) and ECLIA (41·79 pg/mL), SENSORS (243·03 fg/mL) showed 448 times and 172 times improvements, respectively. In the three retrospective validation sets, the SENSORS-based diagnostic system achieved AUCs of 0·95 (95% CI 0·90-0·99) in the SYSUCC internal validation set, 0·93 (0·89-0·97) in the HNCH external validation set, and 0·98 (0·97-1·00) in the CHSUMC external validation set, sensitivities of 87·1% (79·3-92·3), 98·6% (94·4-99·8), and 93·5% (88·1-96·7), and specificities of 88·9% (75·2-95·8), 74·6% (61·3-84·6), and 92·1% (81·7-97·0), respectively, successfully distinguishing between patients with oesophageal squamous cell carcinoma and healthy controls. Additionally, in three prospective validation cohorts, it yielded sensitivities of 90·9% (95% CI 86·1-94·2) for SYSUCC, 84·8% (76·1-90·8) for HNCH, and 95·2% (85·6-98·7) for CHSUMC. Of the six machine-learning algorithms compared, the random forest model showed the best performance. A feature selection step identified five features to have the highest performance to predictions (SCC, age, MMP13, CEA, and NSE) and a simplified random forest model using these five features further improved classification, achieving sensitivities of 98·2% (95% CI 93·2-99·7) in the internal validation set from retrospective SYSUCC cohort I, 94·1% (89·9-96·7) in SYSUCC prospective cohort II, 88·6% (80·5-93·7) in HNCH prospective cohort II, and 98·4% (90·2-99·9) in CHSUMC prospective cohort II. INTERPRETATION: The SENSORS system facilitates highly sensitive detection of oesophageal squamous cell carcinoma tumour biomarkers, overcoming the limitations of detecting low-abundance circulating proteins, and could substantially improve oesophageal squamous cell carcinoma diagnostics. This method could act as a minimally invasive screening tool, potentially reducing the need for unnecessary endoscopies. FUNDING: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Enterprises Joint Fund-Key Program of Guangdong Province. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Value of percentage of highly fluorescent lymphocytic cells for rapidly assessing septicemia in tumor patients].

OBJECTIVE: To evaluate the value of percentage of highly fluorescent lymphocytic cells (HFLC%) for rapidly assessing septicemia in tumor patients. METHODS: Blood samples were collected from 130 patients with tumors (60 septicemia patients and 70 non-septicemia patients) and 80 healthy controls. HFLC% was analyzed with Sysmex XE-5000, the level of C-reactive protein (CRP) measured with a commercially available turbidimetric immunoassay kit and the level of procalcitonin (PCT) determined with a semiquantitative chromatographic immunoassay kit. The diagnostic values of HFLC% and CRP in septicemia were evaluated with ROC analysis. RESULTS: The values of HFLC% and CRP were significantly higher in the septicemia group than those in the non-septicemia and healthy groups (0.30% (0.10%-0.70%) vs 0.10% (0-0.20%), 0.10% (0-0.20%) ; 80.3 (28.5-129.5) vs 3.3 (1.4-41.4) , 1.4 (0.6-2.5) mg/L, all P < 0.01) . The ROC-AUCs for HFLC% and CRP for a diagnosis of septicemia were 0.72 (sensitivity 71.7%, specificity 58.7%) and 0.92 (sensitivity 96.7%, specificity 82.0%). Both of them could judge septicemia better. Additionally, HFLC% was correlated with the levels of PCT and CRP (r = 0.637, 0.241, both P < 0.01). CONCLUSIONS: HFLC% may be used as a rapid and simple auxiliary indicator in the diagnosis of septicemia in patients with tumors. And it is conducive to make an early diagnosis of septicemia and avoid unnecessary use of antibiotics.

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer.

Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 µmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621-0.757; C-index for OS: 0.728, 95% CI: 0.654-0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

The prognostic value of integration of pretreatment serum amyloid A (SAA)-EBV DNA (S-D) grade in patients with nasopharyngeal carcinoma.

BACKGROUND: Serum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA-EBV DNA (S-D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S-D grade was calculated based on the cut-off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S-D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S-D grade with TNM staging system using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S-D grade was divided into S-D grade 1, S-D grade 2, and S-D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices. CONCLUSIONS: We found that the S-D grade could be used as a new tool to predict the OS in NPC patients.

Target-induced proximity ligation triggers recombinase polymerase amplification and transcription-mediated amplification to detect tumor-derived exosomes in nasopharyngeal carcinoma with high sensitivity.

Tumor-derived exosomes (TEXs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. Substantial evidence has implicated TEXs as attractive diagnostic markers for cancer. However, the detection of TEXs in blood at an early tumor stage is challenging due to their very low concentration. Here, we established a method called PLA-RPA-TMA assay that allows TEXs to be detected with high sensitivity and specificity. Based on two proximity ligation assay (PLA) probes that recognize a biomarker on a TEX, we generated a unique surrogate DNA signal for the specific biomarker, which was synchronously amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA), and then the products of the RPA-TMA reaction were quantitatively detected using a gold nanoparticle-based colorimetric assay. We established proof-of-concept evidence for this approach using TEXs from nasopharyngeal carcinoma (NPC) cells, with a detection limit of 102 particles/mL, and reported the measurement of plasma Epstein-Barr virus latent membrane protein 1 (LPM1)-positive (LMP1+, accuracy: 0.956) and epidermal growth factor receptor (EGFR)-positive (EGFR+, accuracy: 0.906) TEXs as potent early diagnostic biomarkers for NPC.

Prognostic nomogram for patients with Nasopharyngeal Carcinoma incorporating hematological biomarkers and clinical characteristics.

Predictive models for survival prediction in individual cancer patients following the tumor, node, and metastasis (TNM) staging system are limited. The survival rates of patients who share TNM stage diseases are diversified. Therefore, we established a nomogram in which hematological biomarkers and clinical characteristics for predicting the overall survival (OS) of nasopharyngeal carcinoma (NPC) patients were incorporated. The clinicopathological and follow-up data of 690 NPC patients who were histologically diagnosed histologically at the Sun Yat-sen University Cancer Center between July 2007 and December 2011 were retrospectively reviewed. Data was randomly divided into primary (n = 460) and validation groups (n = 230). Cox regression analysis was used to identify prognostic factors for building the nomogram in primary cohorts. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index) and decision curve, and were compared with the TNM staging system, Epstein-Barr virus DNA copy numbers (EBV DNA), or TMN stage plus EBV DNA. The results were internally validated by assessment of discrimination and calibration using the validation cohorts at the same institution. Independent factors selected into the nomogram for OS included age [hazard ratio (HR): 1.765; 95% confidence interval (CI): 1.008-3.090)], TNM stage (HR: 1.899; 95% CI: 1.023-3.525), EBV DNA (HR: 1.322; 95% CI: 1.087-1.607), lactate dehydrogenase level (LDH) (HR: 1.784; 95% CI: 1.032-3.086), high sensitivity C-reactive protein (hs-CRP) (HR: 1.840; 95% CI: 1.039-3.258), high-density lipoprotein cholesterol (HDL-C) (HR: 0.503; 95% CI: 0.282-0.896), hemoglobin (HGB) (HR: 0.539; 95% CI: 0.309-0.939) and lymphocyte to lymphocyte ratio (LMR) (HR:0.531; 95% CI: 0.293-0.962). The C-index in the primary cohort and validation cohort were 0.800 and 0.831, respectively, and were statistically higher when compared to C-index values for TNM stage (0.672 and 0. 716), EBV DNA (0.668 and 0.688), and TNM stage+ EBV DNA (0. 732 and 0. 760), P < 0.001 for all. Moreover, the decision curve analyses demonstrated that the nomogram model had a higher overall net benefit compared to the TNM staging system, EBV DNA and TNM stage+ EBV DNA. Next, patients were divided into three distinct risk groups for OS based on total points (TPs) of the nomogram: a low-risk group (TPs ≤ 19.0), an intermediate risk group (19.0 < TPs ≤ 25.5) and a high risk group (TPs > 25.5), respectively. The nomogram predicting prognosis generated for NPC patients had a higher predictive power compared to the TNM staging system, EBV DNA, and TNM stage+ EBV DNA.

Prognostic value of C-reactive protein/albumin ratio in predicting overall survival of Chinese cervical cancer patients overall survival: comparison among various inflammation based factors.

Background: Many studies have shown the prognostic value of inflammation based factors in different cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin (CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors, such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and squamous cell carcinoma antigen (SCC-Ag). Methods: This study was a retrospective analysis of the data related to 229 patients with newly diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by Chi-Square or Fisher's exact test. Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR = 2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone. Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition, NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation was present among SCC-Ag, NLR and CRP/Alb ratio. Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common histological SCC subtypes.

Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China.

In this study, we aimed to use the combined detection of multiple antibodies against Epstein-Barr virus (EBV) antigens to develop a model for screening and diagnosis of nasopharyngeal carcinoma (NPC). Samples of 300 nasopharyngeal carcinoma patients and 494 controls, including 294 healthy subjects (HC), 99 non-nasopharyngeal carcinoma cancer patients (NNPC), and 101 patients with benign nasopharyngeal lesions (BNL), were incubated with the EUROLINE Anti-EBV Profile 2, and band intensities were used to establish a risk prediction model. The nasopharyngeal carcinoma risk probability analysis based on the panel of VCAgp125 IgA, EBNA-1 IgA, EA-D IgA, EBNA-1 IgG, EAD IgG, and VCAp19 IgG displayed the best performance. When using 26.1% as the cutoff point in ROC analysis, the AUC value and sensitivity/specificity were 0.951 and 90.7%/86.2%, respectively, in nasopharyngeal carcinoma and all controls. In nasopharyngeal carcinoma and controls without the non-nasopharyngeal carcinoma and BNL groups, the AUC value and sensitivity/specificity were 0.957 and 90.7%/88.1%, respectively. The diagnostic specificity and sensitivity of the EUROLINE Anti-EBV Profile 2 assay for both nasopharyngeal carcinoma and early-stage nasopharyngeal carcinoma were higher than that of mono-antibody detection by immune-enzymatic assay and real-time PCR (EBV DNA). In the VCA-IgA-negative group, 82.6% of nasopharyngeal carcinoma patients showed high probability for nasopharyngeal carcinoma, and the negative predictive value was 97.1%. In the VCA-IgA-positive group, 73.3% of healthy subjects showed low probability. The positive predictive value reached 98.2% in this group. The nasopharyngeal carcinoma risk probability value determined by the EUROLINE Anti-EBV Profile 2 might be a suitable tool for nasopharyngeal carcinoma screening. Cancer Prev Res; 10(9); 542-50. ©2017 AACR.

Antiparasitic efficacy of curcumin from Curcuma longa against Ichthyophthirius multifiliis in grass carp.

Ichthyophthirius multifiliis is a ciliated parasite that elicits great economic losses in aquaculture. In the present study, a polyphenol compound, curcumin, was obtained from the rhizome of Curcuma longa by bioassay-guided isolation based on the efficacy of anti-I. multifiliis theronts. Anti-I. multifiliis efficacy of curcumin was evaluated in vitro and in vivo. Curcumin resulted in 100% mortality of I. multifiliis theronts at a concentration of 1mg/L within 21.7±1.2min and killed all tomonts at 8mg/L within 31.0±1.0min. Curcumin at 4mg/L for 16h exposure can completely terminate the reproduction of tomonts. The pretreatment with curcumin at concentrations of 0.5, 0.25, and 0.125mg/L for 2h significantly reduced the infectivity of I. multifiliis theronts. Curcumin at 4mg/L completely cured the infected grass carp and protected naive fish from I. multifiliis infection after 10days exposure. The 4h median effective concentration (EC50) of curcumin to I. multifiliis theronts and the 5h EC50 of curcumin to I. multifiliis tomonts were 0.303mg/L and 2.891mg/L, respectively. The 96h median lethal concentration (LC50) of curcumin to grass carp was 56.8mg/L, which was approximately 187.4 times EC50 of curcumin to theronts and 19.6 times EC50 of curcumin to tomonts. The results demonstrated that curcumin has the potential to be a safe and effective therapeutant for controlling ichthyophthiriasis in aquaculture.

Multivariate Analysis of Prognostic Biomarkers in Surgically Treated Endometrial Cancer.

OBJECTIVE: The aim of this study was to identify biomarkers with prognostic value in the setting of surgically treated endometrial cancer. METHODS: Medical data for 282 patients with surgically treated endometrial cancer were reviewed retrospectively. Preoperative concentrations of six serum biomarkers (CA125, CA15-3, C-reactive protein [CRP], D-dimer [D-D], platelet-to-lymphocyte ratio [PLR], and neutrophil-to-lymphocyte ratio [NLR]) were analysed to determine potential associations with clinicopathologic characteristics and to assess prognostic values separately via Kaplan-Meier method and multivariate Cox regression. RESULTS: In univariate analyses, the 5-year overall survival (OS) rate was 86.5% for a maximum follow-up period of 75 months. High concentrations of CA125, CA15-3, CRP, D-D, PLR, and NLR each proved significantly predictive of poor survival (log-rank test, P<0.01). CRP and D-D were identified as independent prognosticators, using a Cox regression model. Study patients were then stratified (based on combined independent risk factors) into three tiers (P<0.001), marked by 5-year OS rates of 92.1%, 78.4%, and 33.3%. CONCLUSIONS: All serum biomarkers assessed (CA125, CA15-3, CRP, D-D, PLR, and NLR) proved to be valid prognostic indices of surgically treated endometrial cancer. A novel prognostic grouping system, incorporating independent risk factors (CRP and D-D Concentrations), may have merit in assessing these patients preoperatively, providing a biologic basis for improved clinical staging.