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Abstract Background Rare infectious diseases of poverty (rIDPs) involve more than hundreds of tropical diseases, which dominantly affect people living in impoverished and marginalized regions and fail to be prioritized in the global health agenda. The neglect of rIDPs could impede the progress toward sustainable development. This study aimed to estimate the disease burden of rIDPs in 2021, which would be pivotal for setting intervention priorities and mobilizing resources globally. Methods Leveraging data from the Global Burden of Disease Study 2021, the study reported both numbers and age-standardized rates of prevalence, mortality, disability-adjusted life-years (DALYs), years lived with disability, and years of life lost of rIDPs with corresponding 95% uncertainty intervals (UIs) at global, regional, and national levels. The temporal trends between 1990 and 2021 were assessed by the joinpoint regression analysis. A Bayesian age-period-cohort model was used to project the disease burden for 2050. Results In 2021, there were 103.76 million (95% UI: 102.13, 105.44 million) global population suffered from rIDPs with an age-standardized DALY rate of 58.44 per 100,000 population (95% UI: 42.92, 77.26 per 100,000 population). From 1990 to 2021, the age-standardized DALY rates showed an average annual percentage change of − 0.16% (95% confidence interval: − 0.22, − 0.11%). Higher age-standardized DALY rates were dominated in sub-Saharan Africa (126.35 per 100,000 population, 95% UI: 91.04, 161.73 per 100,000 population), South Asia (80.80 per 100,000 population, 95% UI: 57.31, 114.10 per 100,000 population), and countries with a low socio-demographic index. There was age heterogeneity in the DALY rates of rIDPs, with the population aged under 15 years being the most predominant. Females aged 15–49 years had four-times higher age-standardized DALY rates of rIDPs than males in the same age. The projections indicated a slight reduction in the disease burden of rIDPs by 2050. Conclusions There has been a slight reduction in the disease burden of rIDPs over the past three decades. Given that rIDPs mainly affect populations in impoverished regions, targeted health strategies and resource allocation are in great demand for these populations to further control rIDPs and end poverty in all its forms everywhere. Graphical Abstract

Abstract Water ice and other volatiles that accumulated in the Moon’s polar regions are among the top priority targets for lunar exploration, due to their significances in both lunar geology and extraterrestrial resource utilization. Locating suitable landing sites and determining the provenance of sampled/measured surface materials are critical for future landed missions. Here, we map over 800 sites of plains terrains in the Moon’s south polar region, with a total surface area of ~46,000 km2. Orbital measurements and analog studies show that most of these plains have apparently higher albedo and lower iron content than volcanic mare plains, suggesting an origin of ejecta-induced debris flows from distant impact craters, especially from the Schrödinger basin. Our findings suggest that the entire lunar south polar region probably have experienced contributions from distant basin materials. We recommend these plains as priority landing sites for future exploration of lunar polar volatiles and early bombardment history.

IntroductionMigrant workers in China are migrants from the rural to the urban areas who usually work in the cities and return to the countryside after a certain period. Due to China’s strict household registration system, they differ significantly from urban residents’ access to public services. However, at the same time, China’s workers are facing a severe phenomenon of overwork, and the group of migrant workers is even more hard-hit by overwork, which will cause various adverse effects on workers and society and should attract the attention of all sectors of society.MethodsThis paper focuses on the impact of digital financial inclusion on the overwork of migrant workers. This study considered cross-sectional data containing 98,047 samples based on the 2017 China Migrants Dynamic Survey 2017 (CMDS) and China Municipal Statistical Yearbook after robustness tests and heterogeneity analysis using probit models.Results(1) digital financial inclusion can effectively alleviate overwork among migrant workers; (2) the impact of digital finance on overwork is more significant for the new generation, digitized industries, and self-employed migrant workers; it is also more significant for the South, East, and small and medium-sized cities than for the North, the Midwest, and large cities; (3) job quality and income are crucial factors in how digital financial inclusion affects overwork among migrant workers. Digital financial inclusion can improve the quality of employment for migrant workers and alleviate overwork. However, the income substitution effect partially reduces the inhibitory impact of digital financial inclusion on overwork.ConclusionContinuously promote the development of digital inclusive finance, improve laws and regulations, and protect the labor rights and interests of migrant workers. At the same time, vocational training and skills upgrading for rural migrant workers should be strengthened to improve the quality of their employment so that they can leave the secondary labor market and enter the primary labor market.

Tumor suppressor PTEN was aberrant silenced in gastric cancer (GC) in our previous study. Activation of PTEN through DNA demethylation is a potential strategy for the treatment of GC. Procyanidin B2 (PB2), an effective DNMT inhibitor, exert positive effects on various diseases. In our work, PB2 suppressed cell proliferation and migration while inducing cell apoptosis in vitro, and inhibited tumorigenesis and development in vivo. PB2 hypomethylated and reactivated PTEN expression via targeting and combining with DNMTs. Targeted glucose metabolism and Seahorse analysis showed that PTEN inhibited cell proliferation via HK1-mediated G6P and PFK1-mediated F1,6-2P, and the tumor-suppressor role of PTEN was not dependent on its phosphatase activity. Furthermore, PTEN promoter methylation could be used as a potential marker to predict GC development. This work aimed to investigate whether PB2 inhibit GC by reactivating PTEN’s tumor suppressor function, providing a powerful tool in the development of medical and editable natural compounds.

China’s health system is facing severe challenges from social transition and the double burden of population aging and non-communicable diseases. Addressing the tension between the public’s increasing demand for health services and the limited availability of medical resources has become a critical issue for health care policymakers and medical insurance fund administrators. In promoting its medical insurance system reform, China is actively developing health technology assessment (HTA) with principles and applications adapted to the Chinese context. This study aims to analyze the evolution of HTA in China with a focus on context, actors, process, content, and challenges encountered through applying a modified verson of Walt and Gilson’s policy triangle framework. Currently, HTA plays an indispensable part in the reform of China’s health care and medical insurance system, especially in the formulation and adjustment of the National Reimbursement Drug List (NRDL). While HTA is increasingly used in China, there remain challenges, such as the slow development of HTA related disciplines, lack of an independent national HTA authority, and limited scope in the use of HTA. Despite the identified challenges, HTA has the potential to support a wide range of applications in China’s health care sector, building on the progress achieved over the last three decades.

The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors. Here, we discuss the mutual influences between glucose deprivation and other features of the tumor microenvironment, such as hypoxia, immune escape, low pH, and oxidative stress. In the face of a series of stress responses brought by glucose deficiency, different types of tumors have different coping mechanisms. We summarize the tumor studies on glucose deficiency in the last decade and review the genes and pathways that determine the fate of tumors under harsh conditions. It turns out that most of these genes help tumor cells survive in glucose-deprivation conditions. The development of related inhibitors may bring new opportunities for the treatment of tumors.

Abstract Background Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis. Methods Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I 2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith’s plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results. Results A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74–1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72–0.90) and disease-free survival (HR 0.83, 95%CI: 0.67–0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract. Conclusions In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.

IntroductionA higher risk for depression and mortality is associated with the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII). The roles of DII in the risk of depression and death in cancer survivors were unclear. We aimed to examine the association between energy-adjusted DII (E-DII) score and risk of depression, and mortality using data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES), with a special focus on cancer survivors.MethodsThe 24-h dietary recall interview was used as a basis to calculate the E-DII score and the Patient Health Questionnaire-9 (PHQ-9) was used to measure the depressive outcomes. Logistic regression analyses were performed to determine the association between quartiles of E-DII score and depression. Cox proportional hazard regression and competing risk analyses were used to estimate the risks of quartiles of E-DII score or depression on mortality.ResultsA total of 27,447 participants were included; including 24,694 subjects without cancer and 2,753 cancer survivors. The E-DII score and depression were not distributed differently between the two groups. However, the E-DII scores were positively associated with within each group’s depression (all P trend < 0.001) and participants with higher E-DII scores had a higher risk of depression (subjects without cancer: ORQ4vsQ1: 2.17, 95% CI: 1.75–2.70; cancer survivors: ORQ4vsQ1: 1.78, 95% CI: 1.09–2.92). The median follow-up time were 87 person-months, a total of 1,701 (4.8%) and 570 (15.2%) all-cause deaths in subjects without cancer and cancer survivors were identified by the end of 2019. The highest E-DII scores quartile was associated with the highest risk of all-cause (HRQ4vsQ1: 1.90, 95% CI: 1.54–2.35) and cardiovascular disease (CVD) cause death (HRQ4vsQ1: 2.50, 95% CI: 1.69–2.3.7) in the subjects without cancer. Moreover, participants with depressive symptoms had higher all-cause mortality (HR: 1.29, 95% CI: 1.04–1.59). No significant correlation was found for E-DII scores or depression with all-cause, cancer-cause or CVD-cause mortality in cancer survivors.ConclusionOur findings demonstrate that E-DII score was positively associated with depression risk. A higher E-DII score or depressive symptom may increase the risks of all-cause and CVD-cause mortality only among general subjects.

Food consumption induces oxidative stress in humans, but the changes in oxidative stress levels after a regular meal are still unclear. We conducted an experimental study on 20 healthy volunteers (10 males, 10 females), who matched in age (±2 years). They were given a regular diet (total energy of 704 kcal, which contains 75 g of carbohydrates, 35 g of protein, and 29 g of lipids) at 11:30 a.m. after a fast of over 12 h. We collected 6-repeated measures of venous blood samples at 2-h intervals via heparin anticoagulant tubes immediately after the meal (indicated as “0” h) and up to 10 h post-consumption. Biomarkers included plasma fluorescent products, plasma malondialdehyde, plasma total antioxidant capacity, and plasma superoxide dismutase. FlOPs were measured at three excitation/emission wavelengths (FlOP_320, FlOP_360, and FlOP_400). The average age and BMI for the twenty participants were 22.70 ± 1.98 years and 20.67 ± 2.34 kg/m2, respectively. Within 10 h after the meal, the overall trend of FlOPs were generally similar. There was no evidence of dose response for any of the three FlOPs (all P > 0.05). However, levels of MDA decreased with the time of fasting (Plinear and Pquadratic < 0.05), with the biggest decrease occurring between 0 and 2 h post-meal. The overall trend of T-AOC and SOD levels also decreased with fasting time (Plinear and Pquadratic < 0.05), though an increase was observed between 0 and 2 h following consumption. Levels of MDA, T-AOC, and SOD but not FlOPs, decreased with fasting time.

In the context of China’s new urbanization construction, it is crucial to deal with the issue of migrants. While land finance, as an essential means of local government financing in China over the past three decades, has made important contributions to China’s economic growth, the impact of land finance on the settlement intentions of migrants still needs to be studied. This study considered cross-sectional data containing 78,642 samples based on the 2017 China Migrants Dynamic Survey 2017 (CMDS) and China Land and Resources Statistical Yearbook. In addition, a binary choice model was constructed, and the impact of the degree of land finance on the settlement intentions of migrants for the prefecture-level cities in China was empirically analyzed. With the help of the mediating- and moderating-effect models, the impact of the degree of land finance on the settlement intentions of migrants was examined from the perspectives of housing pressure, social security, and housing property rights. The results show the following: (1) The higher the degree of land finance, the lower the settlement intentions of migrants. (2) Land finance’s effect on settlement intentions is stronger for urban domiciles, low-skilled laborers, in large cities, and eastern and southern cities in these samples. (3) The higher the degree of land finance, the greater the housing pressure on the migrants, further reducing the settlement intentions of these individuals. However, social security and homeownership can reduce the negative effect of land finance on the settlement intentions of migrants. This paper provides policy implications for the construction of new urbanization and the realization of modernization.

Bud dormancy, which enables damage from cold temperatures to be avoided during winter and early spring, is an important adaptive mechanism of deciduous fruit trees to cope with seasonal environmental changes and temperate climates. Understanding the regulatory mechanism of bud break in fruit trees is highly important for the artificial control of bud break and the prevention of spring frost damage. However, the molecular mechanism underlying the involvement of MYB TFs during the bud break of peach is still unclear. In this study, we isolated and identified the PpMYB52 (Prupe.5G240000.1) gene from peach; this gene is downregulated in the process of bud break, upregulated in response to ABA and downregulated in response to GA. Overexpression of PpMYB52 suppresses the germination of transgenic tomato seeds. In addition, Y2H, Bimolecular fluorescence complementation (BiFC) assays verified that PpMYB52 interacts with a RING-type E3 ubiquitin ligase, PpMIEL1, which is upregulated during bud break may positively regulate peach bud break by ubiquitination-mediated degradation of PpMYB52. Our findings are the first to characterize the molecular mechanisms underlying the involvement of MYB TFs in peach bud break, increasing awareness of dormancy-related molecules to avoid bud damage in perennial deciduous fruit trees.

Abstract Background Hospital-acquired bloodstream infection (BSI) is associated with high morbidity and mortality and increases patients’ length of stay (LOS) and hospital charges. Our goals were to calculate LOS and charges attributable to BSI and compare results among different models. Methods A retrospective observational cohort study was conducted in 2017 in a large general hospital, in Beijing. Using patient-level data, we compared the attributable LOS and charges of BSI with three models: 1) conventional non-matching, 2) propensity score matching controlling for the impact of potential confounding variables, and 3) risk set matching controlling for time-varying covariates and matching based on propensity score and infection time. Results The study included 118,600 patient admissions, 557 (0.47%) with BSI. Six hundred fourteen microorganisms were cultured from patients with BSI. Escherichia coli was the most common bacteria (106, 17.26%). Among multi-drug resistant bacteria, carbapenem-resistant Acinetobacter baumannii (CRAB) was the most common (42, 38.53%). In the conventional non-matching model, the excess LOS and charges associated with BSI were 25.06 days (P

Abstract Background Knee osteoarthritis is a common cause of musculoskeletal pain and a leading cause of disability and healthcare economic burden. The optimum treatment for knee osteoarthritis is still inconclusive. A network meta-analysis is required to assess the efficacy and safety of treatments and provide more scientific medical evidence. Methods Relevant studies were searched through PubMed, Embase, and Cochrane Library electronic databases from the inception to October 2018. Continuous outcomes such as pain, stiffness, physical function and total scores were expressed as the mean differences with 95% credible interval. Surface under the cumulative ranking curve illustrated the rank probability of each therapy under different outcomes. Results Nineteen studies were included in this study, with a total of 2395 patients. For knee pain, platelet-rich plasma (0.691) was ranked at the first place, followed by hyaluronic acid combined with platelet-rich plasma (0.670) and hyaluronic acid (0.402). In terms of stiffness, hyaluronic acid combined with platelet-rich plasma (0.743) enjoyed the highest value, platelet-rich plasma (0.603) was the next and hyaluronic acid (0.386) was the third. As for physical function, the rank was hyaluronic acid combined with platelet-rich plasma (0.772), platelet-rich plasma (0.608) and hyaluronic acid (0.343). For total scores, the order given by surface under the cumulative ranking was hyaluronic acid combined with platelet-rich plasma (0.765), platelet-rich plasma (0.624) and hyaluronic acid (0.37). Conclusions Hyaluronic acid combined with platelet-rich plasma showed the best efficacy in improving stiffness, physical function, and total scores, while platelet-rich plasma appeared the best in terms of pain reduction.

Drought stress is a serious abiotic stress source that affects the growth and fruit quality of peach trees. However, the molecular mechanism of the NUDIX hydrolase family in peaches in response to drought stress is still unclear. Here, we isolated and identified the PpNUDX8 (Prupe.5G062300.1) gene from the peach NUDIX hydrolase family, and found that PpNUDX8 has a typical NUDIX hydrolase domain. In this study, we performed 15% PEG6000 drought treatment on peach seedlings, and qRT–PCR analysis showed that 15% PEG6000 induced the transcription level of PpNUDX8. Overexpression of PpNUDX8 reduced the tolerance of calli to 4% PEG6000 treatment. Compared with wild-type apple calli, PpNUDX8 transgenic apple calli had a lower fresh weight and higher MDA content. After 15% PEG6000 drought treatment, PpNUDX8 transgenic tobacco had a greater degree of wilting and shorter primary roots than Under control conditions. The chlorophyll, soluble protein, and proline contents in the transgenic tobacco decreased, and the MDA content and relative conductivity increased. At the same time, PpNUDX8 negatively regulated ABA signal transduction and reduced the transcriptional expression of stress response genes. In addition, PpNUDX8 was not sensitive to ABA, overexpression of PpNUDX8 reduced the expression of the ABA synthesis-related gene NCED6 and increases the expression of the ABA decomposition-related gene CYP1 in tobacco, which in turn leads to a decrease in the ABA content in tobacco. In addition, Under control conditions, overexpression of PpNUDX8 destroyed the homeostasis of NAD and reduced nicotinamide adenine dinucleotide (NADH) in tobacco. After 15% PEG6000 drought treatment, the changes in NAD and NADH in PpNUDX8 transgenic tobacco were more severe than those in WT tobacco. In addition, PpNUDX8 also interacted with PpSnRk1γ (Prupe.6G323700.1).

Terpene synthase (TPS) is related to the production of aromatic substances, but there are few studies on the impact of abiotic stress on TPS and its molecular mechanism, especially in peaches. This study found that salt resistance and abscisic acid (ABA) sensitivity of transgenic tomatoes were enhanced by overexpression of PpTPS1. Moreover, it was found that PpTPS1 interacted with and antagonized the expression of the bZIP transcription factor ABA INSENSITIVE 5 (PpABI5), which is thought to play an important role in salt suitability. In addition, PpTCP1, PpTCP13, and PpTCP15 were found to activate the expression of PpTPS1 by yeast one-hybrid (Y1H) and dual-luciferase assays, and they could also be induced by ABA. In summary, PpTPS1 may be involved in the ABA signaling regulatory pathway and play an important role in salt acclimation, providing a new reference gene for the improvement of salt resistance in peaches.

High-temperature and high-light are the main adversity stresses faced by strawberry seedlings and open-field cultivation in summer. Chitosan (CTS) is widely used in agriculture as a soil amendment, plant growth regulator, and promoter of cold resistance. However, the effects of CTS on strawberry seedlings under the combined stress of high-temperature and high-light are unclear. This study aimed to determine the effect of CTS on strawberry seedlings under the combined stress of high-temperature and high-light. In this study, Xuelixiang strawberry was used as the experimental plant material. The leaves were sprayed with 100 mg/Kg CTS or deionized aqueous solution and placed under high-temperature and high-light (38 °C, 1800 μ mol·m−2·s−1, respectively) for 8 h. In addition, a suitable temperature and light (23 °C, 400 μ mol·m−2·s−1, respectively) was sprayed with deionized water as a control. The results showed that compared with non-CTS treatment, the chlorophyll (Chl) content in strawberry plants increased by 16.9% after CTS treatment; the net CO2 exchange (Pn) increased by 74.9%; and the maximum photochemical efficiency increased by 20.1%. In addition, CTS treatment increased the content of antioxidants; increased osmotic adjustment substances; improved the activity of reduced glutathione with reduced ascorbic acid (AsA-GSH) circulating antioxidant enzymes; removed reactive oxygen species in plants in time; and reduced the damage of reactive oxygen species to photosynthetic organs and cell membranes, thereby reducing high-temperature and high-light injury to strawberry seedlings. This study shows that CTS can improve the negative effects of high-temperature and high-light stress on strawberry seedlings.

Consumption of dietary lignans has been associated with reduced risk of chronic diseases, although the underlying mechanisms are unclear. We sought to determine if urinary excretion of ENL, the predominant microbial metabolite of dietary lignans, was associated with plasma protein abundance using a cross-sectional design based on data and plasma collected from 80 healthy participants in a randomized crossover, controlled feeding study. Proteomic analysis was performed on plasma samples collected at the end of each of two diet periods (160 samples total) using a customized antibody array corresponding to 2072 unique proteins. GC-MS was used to measure ENL excretion in 24-h urine samples collected in tandem with plasma. Linear mixed models tested the association between urinary enterolignan excretion and plasma protein abundance. Subsequently, over-representation analysis was conducted considering 17 a priori pathways with putative associations with enterolignan bioactivity in an exploratory approach. Controlling the false discovery rate at 10%, ENL excretion was inversely associated with seven proteins (FCRL5, PSCA, GAB1, LAPTM5, CCS, REG4, CEACAM1), and positively associated with two proteins (WAS and FBLN5). Over-representation analysis revealed associations of ENL excretion with estrogen and TNF signaling pathways, which were not significant after adjustment for false discovery. These ENL-associated proteins and pathways have potential implications in cancer prevention.

Abstract Background To quantify the five year incidence trend of all healthcare-associated infections (HAI) using a real-time HAI electronic surveillance system in a tertiary hospital in Beijing, China. Methods The real-time surveillance system scans the hospital’s electronic databases related to HAI (e.g. microbiological reports and antibiotics administration) to identify HAI cases. We conducted retrospective secondary analyses of the data exported from the surveillance system for inpatients with all types of HAIs from January 1st 2013 to December 31st 2017. Incidence of HAI is defined as the number of HAIs per 1000 patient-days. We modeled the incidence data using negative binomial regression. Results In total, 23361 HAI cases were identified from 633990 patients, spanning 6242375 patient-days during the 5-year period. Overall, the adjusted five-year HAI incidence rate had a marginal reduction from 2013 (4.10 per 1000 patient days) to 2017 (3.62 per 1000 patient days). The incidence of respiratory tract infection decreased significantly. However, the incidence rate of bloodstream infections and surgical site infection increased significantly. Respiratory tract infection (43.80%) accounted for the most substantial proportion of HAIs, followed by bloodstream infections (15.74%), and urinary tract infection (12.69%). A summer peak in HAIs was detected among adult and elderly patients. Conclusions This study shows how continuous electronic incidence surveillance based on existing hospital electronic databases can provide a practical means of measuring hospital-wide HAI incidence. The estimated incidence trends demonstrate the necessity for improved infection control measures related to bloodstream infections, ventilator-associated pneumonia, non-intensive care patients, and non-device-associated HAIs, especially during summer months.

Oral cavity squamous cell carcinoma (OCC) and oropharyngeal squamous cell carcinoma (OPC) are among the most common cancers worldwide and are associated with high mortality and morbidity. The purpose of this study is to identify potential biomarkers to distinguish OCC/OPC from normal controls and to distinguish OCC patients with and without nodal metastasis. We tested saliva samples from 101 OCC, 58 OPC, and 35 normal controls using four analytical platforms (NMR, targeted aqueous by LC-MS/MS, global aqueous and global lipidomics by LC-Q-TOF). Samples from OCC and normal controls were divided into discovery and validation sets. Using linear regression adjusting for age, sex, race and experimental batches, we found the levels of two metabolites (glycine and proline) to be significantly different between OCC and controls (FDR < 0.1 for both discovery and validation sets) but did not find any appreciable differences in metabolite levels between OPC and controls or between OCC with and without nodal metastasis. Four metabolites, including glycine, proline, citrulline, and ornithine were associated with early stage OCC in both discovery and validation sets. Further study is warranted to confirm these results in the development of salivary metabolites as diagnostic markers.

Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21-45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value

Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo.Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.ClinicalTrials.gov NCT01682694.

Oral squamous cell cancer of the oral cavity and oropharynx (OSCC) is associated with high case-fatality. For reasons that are largely unknown, patients with the same clinical and pathologic staging have heterogeneous response to treatment and different probability of recurrence and survival, with patients with Human Papillomavirus (HPV)-positive oropharyngeal tumors having the most favorable survival. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we used Affymtrix 6.0 SNP arrays to examine paired DNA from peripheral blood and tumor cell populations isolated by laser capture microdissection to assess genome-wide loss of heterozygosity (LOH) and DNA copy number aberration (CNA) and their associations with risk factors, tumor characteristics, and oral cancer-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p and 11q that seem to play an important role in oral cancer biology and survival from this disease. If confirmed, these findings could assist in designing personalized treatment or in the creation of models to predict survival in patients with HPV-negative OSCC.

Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = -0.308, p = 0.042; glucose: r = -0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = -0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = -0.373, p = 0.016; females: r = -0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.

In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)