Interaction among homeodomain transcription factors mediates ethylene biosynthesis during pear fruit ripening.

Fruit ripening is manipulated by the plant phytohormone ethylene in climacteric fruits. While the transcription factors (TFs) involved in ethylene biosynthesis and fruit ripening have been extensively studied in tomato, their identification in pear remains limited. In this study, we identified and characterized a HOMEODOMAIN TF, PbHB.G7.2, through transcriptome analysis. PbHB.G7.2 could directly bind to the promoter of the ethylene biosynthetic gene, 1-aminocyclopropane-1-carboxylic acid synthase (PbACS1b), thereby enhancing its activity and resulting in increased ethylene production during pear fruit ripening. Yeast-two-hybrid screening revealed that PbHB.G7.2 interacted with PbHB.G1 and PbHB.G2.1. Notably, these interactions disrupted the transcriptional activation of PbHB.G7.2. Interestingly, PbHB.G1 and PbHB.G2.1 also bind to the PbACS1b promoter, albeit different regions from those bound by PbHB.G7.2. Moreover, the regions of PbHB.G1 and PbHB.G2.1 involved in their interaction with PbHB.G7.2 differ from the regions responsible for binding to the PbACS1b promoter. Nonetheless, these interactions also disrupt the transcriptional activation of PbHB.G1 and PbHB.G2.1. These findings offer a new mechanism of ethylene biosynthesis during climacteric fruit ripening.

Optimization and Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the Guangdong Randomized Trial.

BACKGROUND: Screening with anti-Epstein-Barr Virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. METHODS: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women age 30-69). Seropositive subjects were rescreened annually for five years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial sub-cohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. RESULTS: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per-capita). Screening for 5-15 years between ages 35-59 met a willingness-to-pay threshold of 1.5 GDP/QALY in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One lifetime screen could reduce NPC mortality by pproximately 20%. CONCLUSIONS: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. IMPACT: These findings support population-based screening in southern China by defining the target population, cost effectiveness, and optimized screening approach.

18F-FDG PET/CT of Intracholecystic Papillary Neoplasm in Cystic Neck and Duct.

ABSTRACT: We report 18F-FDG PET/CT appearances of intracholecystic papillary neoplasm (ICPN) in the gallbladder neck and duct of a 74-year-old woman with a history of hepatitis B cirrhosis. The lesion presented with a large and sessile soft mass in the neck and duct of gallbladder with obvious glucose metabolism on PET/CT images, which was confirmed pathologically as ICPN (gastric foveolar type) with high-grade intraepithelial neoplasia. ICPN localized in the gallbladder neck and duct is extremely rare, and is easily misdiagnosed as gallbladder carcinoma. Our report aids in the application of PET/CT in the differential diagnosis of ICPN and guiding early surgery.

[Characteristics and Identification Priority Source of Heavy Metals Pollution in Farmland Soils in the Yellow River Basin].

Assessments of the soil environmental quality of farmland and pollution source apportionment are the foundation for ensuring national food security and agricultural sustainable development, as well as an important prerequisite for the pursuit to keep our lands clean. This study evaluated the characteristics of heavy metal pollution in farmland soils in the Yellow River Basin from 2000 to 2023, based on the data of heavy metal contents including As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, using the geo-accumulation index method. Source apportionment was conducted by employing a positive matrix factorization (PMF) model. The probabilistic health risks were evaluated by coupling Monte Carlo simulation with a human health risk assessment model, and priority pollution sources and elements were identified. The results showed that:① the average content of all heavy metals in farmland soils within the study area was lower than the screening values specified in the soil environment quality risk control standard for soil contamination of agriculture land (GB 15618-2018) (pH>7.5). However, the contents of Cd, As, and Zn in the samples exceeded their screening values, with percentages of 21.69%, 5.56%, and 1.23%, respectively, with Cd having the highest rate of exceedance. ② Hg and Cd were moderately polluted, Cu and Pb were slightly polluted, and the other elements were not polluted. ③ The main sources of heavy metals in farmland soil were traffic-industrial sources, natural-agricultural sources, industrial-natural sources, and agricultural-industrial sources, with contribution rates of 37.04%, 26.69%, 21.72%, and 14.55%, respectively. ④ Heavy metals in farmland soil posed carcinogenic health risks to adults and children but did not have non-carcinogenic risks; As and Cd were priority control elements for human health risks, and industrial-natural sources and agricultural-industrial sources were priority control sources in the study area.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Association of Metabolic Syndrome With Risk of Lung Cancer: A Population-Based Prospective Cohort Study.

BACKGROUND: Both the incidence of lung cancer and the prevalence of metabolic syndrome (MetS) have been increasing worldwide. The relationship between MetS and lung cancer remains controversial. RESEARCH QUESTION: What is the risk of lung cancer associated with MetS and its components? STUDY DESIGN AND METHODS: Multivariable Cox regression models were used to estimate the hazard ratio (HR) of MetS-related variables on lung cancer risk, both overall and by histologic subtype, in the UK Biobank. Stratified analyses were conducted by sex, tobacco use status, and use of medication. HR curves were used to test the nonlinear associations between the metabolic markers and the risk of lung cancer. RESULTS: Of the 331,877 participants included in this study, a total of 77,173 participants had a diagnosis of MetS at enrollment. During a median follow-up of 10.9 years, lung cancer as the primary site developed in 2,425 participants. The HRs of MetS were 1.21 (95% CI, 1.09-1.33), 1.28 (95% CI, 1.10-1.50), and 1.16 (95% CI, 0.94-1.44) for the overall risk of lung cancer, adenocarcinoma, and squamous cell carcinoma, respectively. The HRs increased with the number of metabolic abnormalities from 1.11 to approximately 1.4 or 1.5 for those with one to five disorders. Positive association with lung cancer was observed for low high-density lipoprotein cholesterol (HDL-C), elevated waist circumference, and hyperglycemia. The relationship between MetS and lung cancer was modified by sex, with a stronger effect in female patients (P = .031). The risk of lung cancer resulting from MetS was elevated mainly among individuals who used tobacco, although the modification effect of tobacco use was not statistically significant. A nonlinear association was found between lung cancer and HDL-C, waist circumference, and glycated hemoglobin. INTERPRETATION: The increased risk of lung cancer associated with MetS suggests the importance of taking metabolic status and markers into consideration for the primary prevention of lung cancer and the selection of high-risk populations for lung cancer screening.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Blood-nerve barrier enhances chronic postsurgical pain via the HIF-1α/ aquaporin-1 signaling axis.

BACKGROUND: Blood nerve barrier (BNB) participates in the development of neuropathic pain. AQP1 is involved in peripheral pain perception and is negatively correlated with HIF-1α phenotype, which regulates endothelial permeability. However, the role of HIF-1α-AQP1-mediated BNB dysfunction in Chronic Postsurgical Pain (CPSP) has not been reported. METHODS: Male Sprague-Dawley rats were randomized into 5 groups: (i) Naive group; (ii) Sham group; (iii) SMIR group: skin/muscle incision and retraction for one hour. Behavioral tests were performed for the three groups, BNB vascular permeability and western blotting were conducted to determine HIF-1α and AQP1 protein expression. (iv) The SMIR + HIF-1α inhibitor group; (v) SMIR + DMSO group. Rats in the two groups were administered with HIF-1α inhibitor (2ME2) or DMSO intraperitoneally on the third day post-SMIR surgery followed by performance of behavioral tests, BNB permeability assessment, and determination of HIF-1α, AQP1 and NF200 protein levels. RESULTS: The permeability of BNB was significantly increased and the expression of AQP1 was downregulated on the 3rd and 7th days post-operation. AQP1 is mainly located in neurons and NF200, CGRP-positive nerve fibers. HIF-1α was highly expressed on the third day post-operation. HIF-1α inhibitor reversed the decrease in AQP1 expression and increase in NF200 expression, barrier permeability and hyperalgesia induced by SMIR on the 3rd day post-surgery. CONCLUSIONS: Early dysfunction of BNB mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism to promote acute postoperative painful transformation of CPSP. Preadaptive protection of endothelial cells around nerve substructures may be an important countermeasure to inhibit CPSP transformation. Early impairment of BNB function mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism for promoting acute postoperative pain transformation of CPSP.

Mortality among papillary thyroid cancer patients by detection route: a hospital-based retrospective cohort study.

Background: Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients. Methods: We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality. Results: Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04-0.46; P = 0.01) and 0.47 (95% CI: 0.20-1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively. Conclusions: Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

Associations between serum trace elements and the risk of nasopharyngeal carcinoma: a multi-center case-control study in Guangdong Province, southern China.

Background: Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined. Methods: This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein-Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma-mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models. Results: Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation. Conclusion: Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.

Role of the blood-spinal cord barrier: An adheren junction regulation mechanism that promotes chronic postsurgical pain.

Chronic postsurgical pain (CPSP) is a serious postoperative complication with high incidence, and its pathogenesis involves neuroimmune interactions and the breakdown of the blood-spinal cord barrier (BSCB), the decreased level of adheren junction (AJ)-related proteins is an important cause of BSCB injury. Vascular endothelial-cadherin (VE-cadherin) and p120 catenin (p120) constitute the endothelial barrier adheren junction. The Src/p120/VE-cadherin pathway is involved in the regulation of the endothelial barrier function. However, the role of the BSCB-AJ regulatory mechanism in CPSP has not been reported. In this study, we established a skin/muscle incision and retraction (SMIR) model and evaluated the paw withdrawal threshold (PWT), the effects of an Src inhibitor and p120 knockdown on p-Src, p120 and VE-cadherin expression, as well as BSCB-AJ function in rat spinal cord were observed to explore the regulation of BSCB-AJ function by the p-Src/p120/VE-cadherin pathway in promoting SMIR-induced CPSP. The levels of p-Src, p120 and VE-cadherin in the spinal cord were detected by Western blot. Meanwhile, BSCB permeability test was used to detect the changes in BCSB function. Finally, the spatial and temporal localization of p120 in spinal cord was detected by immunofluorescence. Our findings indicated that p-Src/p120/VE-cadherin could induce BSCB-AJ dysfunction and promote the development of CPSP.

Resistin Promotes Nasopharyngeal Carcinoma Metastasis through TLR4-Mediated Activation of p38 MAPK/NF-κB Signaling Pathway.

NPC is a type of malignant tumor with a high risk of local invasion and early distant metastasis. Resistin is an inflammatory cytokine that is predominantly produced from the immunocytes in humans. Accumulating evidence has suggested a clinical association of circulating resistin with the risk of tumorigenesis and a relationship between blood resistin levels and the risk of cancer metastasis. In this study, we explored the blood levels and the role of resistin in NPC. High resistin levels in NPC patients were positively associated with lymph node metastasis, and resistin promoted the migration and invasion of NPC cells in vitro. These findings were also replicated in a mouse model of NPC tumor metastasis. We identified TLR4 as a functional receptor in mediating the pro-migratory effects of resistin in NPC cells. Furthermore, p38 MAPK and NF-κB were intracellular effectors that mediated resistin-induced EMT. Taken together, our results suggest that resistin promotes NPC metastasis by activating the TLR4/p38 MAPK/NF-κB signaling pathways.

CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats.

Purpose: Caveolae (CAV) are an invaginated microcapsule with the shape of Ω on the surface of the cell membrane. Caveolin-1 (CAV-1) is involved in neuropathic pain, and adenosine monophosphate (AMP)-exchange protein directly activated by cAMP1 (EPAC-1) is a potential therapeutic target for chronic pain. However, whether EPAC-1 promotes chronic postsurgical pain (CPSP) through CAV-1 has not been reported. Here, we aim to investigate the underlying mechanism of CAV in CPSP. Methods: All the rats were divided into 9 groups, including the Naive group, Sham group, skin/muscle incision and retraction (SMIR) group, SMIR + CAV-1 siRNA group, SMIR + control siRNA group, SMIR (7 days)+Saline group, SMIR (7 days)+CE3F4 group, 8-PCPT group, and Saline group. The CPSP rat model was established after SMIR. A mechanical withdrawal threshold (MWT) was recorded to evaluate the animal's behavior. Western blotting and immunofluorescent were performed to detect the protein expression levels of EPAC-1 and P-CAV-1. Results: EPAC-1 and CAV-1 were both overexpressed after operation, particularly in astrocytes, microglia, and neurons of spinal marrow (all P < 0.05). Interestingly, CAV-1 siRNA can partly reverse the SMIR-induced hypersensitivity, but there was no effect on EPAC-1. Besides, EPAC-1 blockage partly reversed the SMIR-induced hypersensitivity and CAV-1 overexpression, and EPAC-1 activation promoted CAV-1 overexpression and hypersensitivity in normal rats (all P < 0.05). Conclusion: CAV-1 mediates the functional coupling of microglia, astrocytes, and neurons, and thus EPAC-1/CAV-1 plays an important role in CPSP exacerbation.

Propofol Regulates the Expression of BecliN-1 through miR-30b and Protects against Lung Ischemia-Reperfusion Injury.

Pulmonary ischemia-reperfusion can cause severe dysfunction of alveolar epithelium and alveolar cells. Drugs such as propofol have a protective effect on lung ischemia-reperfusion, but this protective mechanism is not stable and requires other factors such as nucleosides. The purpose of this article is to study the protective mechanism of propofol on lung ischemia-reperfusion injury by regulating the expression of BecliN-1 by miR-30b. With 72 male rats as the research object, a rat lung ischemia-reperfusion model was established. Phenol agents were perfused as the perfusion solution to detect the expression levels of miR-30b and BecliN-1, statistical experimental data and analyze the regulatory mechanism of miR-30b on the expression of BecliN-1 and the effect of propofol on the protection of lung ischemia-reperfusion. Research results show that propofol can reduce inflammation, reduce oxidative stress, inhibit lung tissue apoptosis, improve lung function and pathological changes of lung tissue by inhibiting the activation of the JAK-STAT signaling pathway, and propofol can pass. The protection of miR-30b's regulation of BecliN-1 expression against lung ischemia-reperfusion injury is 30% higher than that of other protective mechanisms. At the same time, the apoptosis rate of inflammatory lung tissue cells is reduced by 13%.

Environmental Factors for Epstein-Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study.

Background: Epstein-Barr virus (EBV) reactivation from latent to lytic infection has been considered as a key step in nasopharyngeal carcinoma oncogenesis. However, epidemiological evidence regarding environmental risk factors for EBV reactivation on a population level remains largely lacking. Methods: We enrolled 1916 randomly selected adults from the general population of Guangdong and Guangxi, China, from 2010 to 2014. Information on environmental factors was collected via a structured interview. Serum immunoglobulin A antibodies against EBV viral capsid antigen and nuclear antigen 1 were measured by enzyme-linked immunosorbent assay to evaluate EBV reactivation status. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of EBV reactivation with various environmental factors. Results: No associations were observed between EBV reactivation and extensive environmental factors, including alcohol or tea drinking, a history of chronic ear/nose/throat diseases, use of medications or herbs, consumption of salted fish or preserved foods, oral hygiene, sibship structure, and various residential and occupational exposures. Only cigarette smoking was associated with EBV reactivation (current smokers vs never smokers; OR = 1.37; 95% CI = 1.02-1.83), with positive exposure-response trends with increasing intensity, duration, and pack-years of smoking. Conclusions: Consistent with previous studies, we found an association between cigarette smoking and EBV reactivation. Other examined exposures were not associated with EBV reactivation. These null results could suggest either more complex interactions between exposures and EBV reactivation or a predominant role of host and/or viral genetic variation.

Association between solid fuel use and seropositivity against Epstein-Barr virus in a high-risk area for nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) is one of the risk factors of nasopharyngeal carcinoma (NPC), and understanding the modifiable risk factors of EBV activation is crucial in the prevention of NPC. In this study, we aimed to investigate the association between solid fuel use and EBV seropositivity in a high-risk area of NPC. Our study was based on the baseline findings from an ongoing population-based prospective cohort in Sihui county in Southern China. We explored the association between current use of solid fuel in cooking and EBV seropositivity, and NPC-related EBV activation, using logistic regression models. Stratification analyses were further conducted to assess potential effect modifiers. We also examined the impact of frequency and duration of solid fuel use, and switch in fuel types, on EBV seropositivity among ever users. Of the 12,579 participants included in our analysis, 4088 (32.5%) were EBV seropositive and 421 (3.3%) were high risk for NPC-related EBV activation. Solid fuel use was associated with a higher risk of EBV seropositivity and NPC-related EBV activation, with odds ratios (ORs) of 1.33 (95%CI: 1.01, 1.76) and 1.81 (95%CI: 1.03, 3.18), respectively. Higher risk of EBV seropositivity was observed for those who did not use ventilation apparatus and those who consumed salted food. Among ever users, OR was highest for participants with more than 40 years of solid fuel exposure (1.17, 95%CI: 1.00-1.37) and who have been constantly using solid fuel (1.30, 95%CI: 0.96-1.75). We did not find a statistically significant impact of cooking frequency on EBV seropositivity. The identification of solid fuel as a risk factor for EBV activation is of great value for understanding the etiology of NPC. Our findings also have important public health implications given the fact that a third of the global population still lack access to clean cooking, especially in low resource settings.

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs.

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

Development and Validation of an Inflammatory Response-Related Gene Signature for Predicting the Prognosis of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly dangerous malignant tumor of the digestive tract, and difficult to diagnose, treat, and predict the prognosis. As we all know, tumor and inflammation can affect each other, and thus the inflammatory response in the microenvironment can be used to affect the prognosis. So far, the prognostic value of inflammatory response-related genes in PAAD is still unclear. Therefore, this study aimed to explore the inflammatory response-related genes for predicting the prognosis of PAAD. In this study, the mRNA expression profiles of PAAD patients and the corresponding clinical characteristics data of PAAD patients were downloaded from the public database. The least absolute shrinkage and selection operator (LASSO) Cox analysis model was used to identify and construct the prognostic gene signature in The Cancer Genome Atlas (TCGA) cohort. The PAAD patients used for verification are from the International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier method was used to compare the overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were performed to identify the independent predictors of OS. Gene set enrichment analysis (GSEA) was performed to obtain gene ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the correlation between gene expression and immune infiltrates was investigated via single sample gene set enrichment analysis (ssGSEA). The GEPIA database was performed to examine prognostic genes in PAAD. LASSO Cox regression analysis was used to construct a model of inflammatory response-related gene signature. Compared with the low-risk group, patients in the high-risk group had significantly lower OS. The receiver operating characteristic curve (ROC) analysis confirmed the signature's predictive capacity. Multivariate Cox analysis showed that risk score is an independent predictor of OS. Functional analysis shows that the immune status between the two risk groups is significantly different, and the cancer-related pathways were abundant in the high-risk group. Moreover, the risk score is significantly related to tumor grade, stage, and immune infiltration types. It was also obtained that the expression level of prognostic genes was significantly correlated with the sensitivity of cancer cells to anti-tumor drugs. In addition, there are significant differences in the expression of PAAD tissues and adjacent non-tumor tissues. The novel signature constructed from five inflammatory response-related genes can be used to predict prognosis and affect the immune status of PAAD. In addition, suppressing these genes may be a treatment option.

Association Between Traditional Herbal Diet and Nasopharyngeal Carcinoma Risk: A Prospective Cohort Study in Southern China.

INTRODUCTION: Prospective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort study in southern China. METHODS: Based on an NPC screening cohort established in 2008-2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30-69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation. RESULTS: During a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15-0.62) for the highest intake frequency and 0.29 (95% CI: 0.16-0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65-0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64-0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59-0.84) for VCA-IgA and 0.64 (95% CI: 0.54-0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals. CONCLUSIONS: With inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas.