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Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.

Background. Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. The purpose of this study is to search for genes related to the prognosis of LUAD through methylation based on a linear mixed model (LMM). Methods. Gene expression, methylation, and survival data of LUAD patients were downloaded from the TCGA database. Based on the LMM model, the GEMMA algorithm was used to screen the predictive genes related to LUAD survival. The Cox model was used to further screen the predicted genes, and then, protein-protein interaction (PPI) network was constructed. Through the software plugin Cytoscape MCODE 3.8.0, the most closely related genes in the PPI network module were selected for in-depth biological function analysis to further explore the interaction and correlation between genes. Results. We screened out 97 predictive genes from 18,834 genes and eliminated one gene associated with lung squamous cell carcinoma from previous studies, leaving 96 genes. The MCODE and the Kaplan-Meier curve analysis were used to finally identify two genes ASB16 and NEDD4 that are related to the prognosis of LUAD. Conclusions. The newly identified two genes associated with the prognosis of LUAD may provide a basis for the treatment of patients.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan–Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.

Vascular endothelial growth factor affects the invasiveness of solid tumors by regulating angiogenesis. However, it is not clear whether VEGF could be used to predict the prognosis of DLBCL in the era of rituximab-based immunotherapy. We conducted a retrospective study to explore response to therapy and the prognostic value of VEGF on DLBCL in the rituximab era. The subjects were 65 patients with a histological diagnosis of DLBCL from the Affiliated Hospital of Xuzhou Medical University. Kaplan-Meier analysis was performed to estimate the cumulative survival rate of patients with different VEGF and IPI levels, and comparisons between groups were made using the log-rank test. DLBCL patients with elevated VEGF were more likely to have extranodal involvement, advanced stage, Myc/Bcl-2 double expression, and a higher Ki-67 score. Elevated VEGF was associated with poor therapeutic response and survival. When patients were divided into low, low-intermediate, high-intermediate and high-risk groups using the V-IPI model based on VEGF and IPI, PFS rates were 94.4, 74.1, 40.6 and 14.8%, respectively. This model better identified low-risk patients than IPI (85.9, 88.9, 37 and 7.8%). Our results demonstrate that VEGF predicts therapeutic response in DLBCL and the V-IPI model accurately predicts PFS of low-risk DLBCL in the rituximab era.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cut-off points of continuous variables; univariate and multivariate Cox analysis were used for variables selection, and Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, brier score and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in derivation and validation cohort by using bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH. Disclosures No relevant conflicts of interest to declare.

Increasing evidence indicates that inflammatory microenvironment facilitates tumor metastasis. Here, we found that LFG-500, a novel synthetic flavonoid, significantly inhibited epithelial–mesenchymal transition (EMT) in human lung adenocarcinoma A549 and H1299 cells co-cultured with LPS-challenged THP-1 cells or cultured in THP-1 cell-derived conditioned medium. Moreover, we found that TNF-α is a direct and decisive factor for promoting EMT and LFG-500 suppressed TNF-α-induced EMT and cell motility. NLRP3 knockdown inactivated NLRP3 inflammasome, which subsequently inhibited EMT and blocked cell migration, indicating that TNF-α-induced EMT requires the NLRP3 inflammasome. LFG-500 inhibited the activation of the NLRP3 inflammasome, thus inhibiting EMT. Moreover, LFG-500 treatment significantly inhibited metastasis in vivo by downregulating NLRP3 expression. Importantly, we found that NLRP3 was highly expressed in high-grade lung adenocarcinoma and that its expression was correlated with lymph node metastasis. NLRP3 and vimentin levels were significantly increased in matched metastatic lymph nodes. Moreover, a significant positive correlation was observed between their levels. Together, these results suggest that LFG-500 markedly suppresses EMT by inhibiting the NLRP3 inflammasome in the inflammatory microenvironment and that NLRP3 is a potential biomarker of lung adenocarcinoma metastasis.

Objective Previous studies have suggested that variations in the ABCC8 gene may be closely associated with T2DM susceptibility and repaglinide response. However, these results have not been entirely consistent, and there are no related studies in a Chinese population, suggesting the need for further exploration. The current study investigated the associations of the ABCC8 rs1801261 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. Methods A total of 234 T2DM patients and 105 healthy subjects were genotyped for ABCC8 rs1801261 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. A total of 70 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take 3 mg repaglinide per day (1 mg each time before meals) for 8 consecutive weeks. The pharmacodynamic parameters of repaglinide and biochemical indicators were then determined before and after repaglinide treatment. Results The frequency of ABCC8 rs1801261 allele was higher in T2DM patients than in the control subjects (22.6% vs.11.0%, p

With rapid industrialization and modernization in China, long-term dietary exposure to cadmium (Cd) has the potential to cause health risks. The traditional probabilistic approach for long-term dietary assessment was a semi-probabilistic method that had limitations in qualifying the variation in concentration data. Thus, this article estimated the long-term dietary exposure to Cd of the adults of Jiangsu province using semi-probabilistic and fully probabilistic approaches, and compared the two models. Cd concentration data were obtained from the national food contamination monitoring program 2001–2009. Food consumption data were gathered from the National Diet and Nutrition Survey conducted in 2002. The provisional tolerable daily intakes (PTDI) of 0.8 μg kg–1 bw for Cd was applied in the risk assessment. The estimates of semi-probabilistic approach were within the provisional tolerable daily intakes (PTDI) at mean and all percentiles. However, the P95 of exposure with fully probabilistic approach...

By synthesizing results from primary studies, systematic review can provide empirical information of concerned problems. This study aimed to review the available surveillance data from studies reporting the contamination surveillance of food lead in China.Relevant studies were identified by systematically searching Chinese Biological Medicine Database and China National Knowledge Infrastructure using the key term of "lead" for surveillance data published in Chinese between 2006 and 2012. To avoid potential selection bias, all articles were evaluated by two independent reviewers, and the disagreements were resolved by discussion or the third author was asked to arbitrate.Among 269 identified publications on surveillance data of lead in food, 43 articles met the defined inclusion criteria. The food samples were divided into 11 groups (cereal grains and pulses, fish, eggs, vegetables, meat, edible fungi, milk and dairy products, fruits, offal, tea and preserved egg). Surveillance data of publications were reviewed to calculate the weighted mean and rate exceeding maximum levels. Our results indicated that the highest lead concentration was 1.937 mg/kg in tea. The total percentage of samples exceeding the maximum levels was 5.57%. Dietary exposure to lead was assessed by combining the weighted mean concentration of surveillance data with national consumption data in 2002. In this review, dietary intake of lead was 1.232 µg/kg b.w./day.Further control measures should be taken to reduce exposure to lead, from both dietary and non-dietary sources.

The paper's main purpose is to estimate the dietary exposure to lead for the inhabitants of Jiangsu province, China. Lead concentration data were obtained from the national food contamination monitoring programme during 2007-10. Food samples (n = 2077) were collected from 23 food categories in Jiangsu province. Consumption data were derived from Chinese national nutrition and health survey in 2002, which included 3938 inhabitants from 1451 households in Jiangsu province. Concentration data were combined with consumption data to estimate the dietary intake for the inhabitants of 2-6, 7-17 and 18-80 years, respectively. The β-binomial-normal (BBN) model was used to estimate the long-term intake for the population in Jiangsu province. The distribution of individual margin of exposure (IMoE) was introduced to assess the health effect. Uncertainty of IMoE was quantified by Monte Carlo and bootstrap methods. The mean levels of dietary exposure to lead were estimated at 3.019 µg kg(-1) bw day(-1) for children aged 2-6 years, 2.104 µg kg(-1) bw day(-1) for teenagers aged 7-17 years, and 1.601 µg kg(-1) bw day(-1) for adults aged 18-80 years. The mean intakes for the urban and rural populations were 1.494 and 1.822 µg kg(-1) bw day(-1), respectively. From the 25th to 99.9th percentiles, IMoE was 0.125-2.057 for 2-6 years and 0.473-7.998 for 18-80 years, respectively. The distribution of IMoE could indicate a public health concern on lead for the Chinese population in Jiangsu. Control measures should be taken to reduce lead exposure in Jiangsu province.