Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.

Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy.

BACKGROUND: Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments. METHODS: We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets. RESULTS: In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells' CXCR1/CXCR2 and neutrophils' CXCL5/CXCL8) of this type. CONCLUSIONS: TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC. Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups. Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses. Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

The survival of esophageal cancer by subtype in China with comparison to the United States.

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the main subtypes of esophageal cancer (EC), but nationwide survival of both EC subtypes has never been reported in China. Our study aimed to estimate the survival trends of EC by subtype in China and compare them with those in the United States for the same period. We used data from 64 Chinese cancer registries, which included EC patients diagnosed during 2008 and 2015 and followed up until 31st December 2017. The 5-year age-standardized relative survival by subtype, sex, age group and urban or rural area between 2008 and 2017 were analyzed. We stratified survival estimates by calendar period (2008-2009, 2010-2011, 2012-2014 and 2015-2017). Data from the SEER 18 program were calculated to estimate the survival of EC in the United States. A further comparison between the survivals in areas covered and not covered by population-based endoscopic screening programs in China was conducted. A total of 129 962 records were included in the survival analyses. Results revealed that age-standardized 5-year relative survivals for AC and SCC increased in both China and the United States from 2008 to 2017. In 2015 to 2017, 5-year survival from both subtypes in China was better than the United States (SCC: 36.9% vs 18.5%, AC: 34.8% vs 22.3%). The survival for both subtypes was significantly higher in screening areas than in nonscreening areas in China (SCC: 40.6% vs 32.8%; AC: 43.0% vs 31.3%). A survival gap in EC by subtype exists between China and the United States. Our results may support the beneficial effect of population-based endoscopic screening for survival, and may be poised to inform national policy-making in both countries.

Synthesis and biological activity assay of novel camptothecin-peptidic conjugates based on PEPT1.

Camptothecin (CPT) and its derivatives are potent candidates for cancer treatment. However, the clinical applications are largely restricted by non-selectivity and severe toxicities. The peptide transporter 1 (PEPT1), which is highly expressed in human intestines, has been found to be overexpressed in several cancer cells. This discovery suggests that PEPT1 has the potential to serve as a therapeutic target for both improving bioavailability and cancer-targeting treatment. Therefore, a prodrug approach for CPT targeting at PEPT1 highly expressed cancer cells was adopted in the present study. Eighteen CPT prodrugs, its peptidic conjugates, were synthesized and the structures were confirmed by NMR and HRMS. The protein expression profiles of PEPT1 in different cell lines were performed using immunofluorescence assay and western blotting analysis. The cytotoxicity of CPT prodrugs and their uptake via competition with Gly-Sar, a typical substrate of PEPT1, were evaluated in both PEPT1-overexpressed and under expressed cells. The results demonstrated that most CPT prodrugs significantly impaired Gly-Sar uptake, suggesting a higher affinity of CPT-peptidic conjugates for PEPT1 and PEPT1 overexpression cells. In addition, these prodrugs demonstrated a higher capability for inhibiting cell growth in PEPT1 highly-expressed cancer cells compared to PEPT1 under expressed cells. These results indicated that this peptidic prodrug strategy might offer great potential for improved tumor selectivity and chemotherapeutic efficacy of CPT.

The occurence of cancer in ageing populations at global and regional levels, 1990 to 2019.

BACKGROUND: population ageing contributes to increased cancer cases and deaths and has profound implications for global healthcare systems. We estimated the trends of cancer cases and deaths in ageing populations at global and regional levels. METHODS: using data from the Global Burden of Disease Study 2019, we analysed the change in cancer cases and deaths associated with population ageing, population growth and epidemiological factors from 1990 to 2019 using decomposition analysis. Additionally, we estimated the proportions of people aged 65 years and over accounting for total cases and deaths, and investigated relationships between the proportions and the Sociodemographic Index (SDI) using the Pearson correlation coefficient. RESULTS: from 1990 to 2019, there was an increase of 128.9% for total cases and 74.8% for total deaths in all cancers combined; the percentages of older people increased from 48.6% to 56.4% for cases and from 52.0% to 61.9% for deaths. Population ageing contributed to the largest increase in global cancer occurrence, with 56.5% for cases and 63.3% for deaths. However, the changes attributed to epidemiological factors was 5.2% for cancer cases and -33.4% for cancer deaths. The proportions of total cases and deaths of older adults were positively correlated with socioeconomic development of the country. CONCLUSION: our findings revealed that the main contributor to increased cancer cases and deaths has changed from comprehensive epidemiological factors to demographic shifts. To respond to the rapidly growing occurrence of cancer in ageing populations, the global health priority should focus on meeting the rising demand for cancer diagnosis, treatment and care services for older people.

Global and national trends in the age-specific sex ratio of esophageal cancer and gastric cancer by subtype.

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age-specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003-2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age-standardized incidence rates (ASIRs) and male-to-female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male-to-female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male-to-female incidence rate ratios increased from young ages, approaching a peak at ages 60-64, but sharply declined thereafter. Similar "low-high-low" trends of age-specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age-dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.

A liquid biopsy signature predicts lymph node metastases in T1 oesophageal squamous cell carcinoma: implications for precision treatment strategy.

BACKGROUND: The treatment strategies for T1 oesophageal squamous cell carcinoma (ESCC) patients with or without lymph node metastasis (LNM) are different. Given the advantages of the minimally invasive, sensitive and real-time detection, liquid biopsy has become an important cancer diagnostic and prognostic tool. METHODS: MiRNA array and small-RNA sequencing were performed. Then, 222 formalin-fixed and paraffin-embedded tumour samples and 229 pretreatment serum samples from T1 ESCC patients were used to verify and evaluate the results. RESULTS: We demonstrated that serum miR-20b-5p could predict LNM in T1 ESCC patients. The AUC for serum miR-20b-5p was higher (0.827) than those for lymphovascular invasion (LVI) (0.751, P = 0.2128), invasion depth (0.662, P = 0.0027) and tumour differentiation grade (0.634, P = 0.0019). A nomogram for predicting LNM with three independent significant predictors (miR-20b-5p, LVI and invasion depth) was constructed with a concordance index of 0.931. Serum miR-20b-5p was also significantly correlated with disease-free survival (P < 0.001). An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level was constructed. CONCLUSIONS: This study suggests that serum miR-20b-5p is a potential biomarker for predicting LNM and can be helpful for precise clinical decision-making strategies and improve treatment outcomes for T1 ESCC patients.

Effects of silicon application on leaf structure and physiological characteristics of Glycyrrhiza uralensis Fisch. and Glycyrrhiza inflata Bat. under salt treatment.

BACKGROUND: Soil salinization leads to a significant decline in crop yield and quality, including licorice, an important medicinal cash crop. Studies have proofed that the application of exogenous silicon can significantly improve the ability of licorice to resist salt stress, however, few studies concentrated on the effects of foliar silicon application on the morphology, physiological characteristics, and anatomical structure of licorice leaves under salt stress. In this study, the effects of Si (K2SiO3) on the structural and physiological characteristics of Glycyrrhiza uralensis Fisch. and G. inflata Bat. leaves under different salt concentrations (medium- and high-salt) were studied. RESULTS: Compared with the control (without salt), the plant height, total dry weight, leaf area, leaf number, relative water content, xylem area, phloem area, ratio of palisade to spongy tissue, gas exchange parameters, and photosynthetic pigment content of both licorice varieties were significantly reduced under high-salt (12S) conditions. However, the thickness of the leaf, palisade tissue, and spongy tissue increased significantly. Applying Si to the leaf surface increased the area of the vascular bundle, xylem, and parenchyma of the leaf's main vein, promoted water transportation, enhanced the relative leaf water content, and reduced the decomposition of photosynthetic pigments. These changes extended the area of photosynthesis and promoted the production and transportation of organic matter. G. uralensis had a better response to Si application than did G. inflata. CONCLUSIONS: In conclusion, foliar application of Si can improve water absorption, enhance photosynthesis, improve photosynthetic capacity and transpiration efficiency, promote growth and yield, and alleviate the adverse effects of salt stress on the leaf structure of the two kinds of licorice investigated.

Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.

Sigma-1 receptor (Sig-1R) is a protein present in several organs such as brain, lung, and heart. In a cell, Sig-1R is mainly located across the membranes of the endoplasmic reticulum and more specifically at the mitochondria-associated membranes. Despite numerous studies showing that Sig-1R could be targeted to rescue several cellular mechanisms in different pathological conditions, less is known about its fundamental relevance. In this review, we report results from various studies and focus on the importance of Sig-1R in physiological conditions by comparing Sig-1R KO mice to wild-type mice in order to investigate the fundamental functions of Sig-1R. We note that the Sig-1R deletion induces cognitive, psychiatric, and motor dysfunctions, but also alters metabolism of heart. Finally, taken together, observations from different experiments demonstrate that those dysfunctions are correlated to poor regulation of ER and mitochondria metabolism altered by stress, which could occur with aging.

Inhibition of MZF1/c-MYC Axis by Cantharidin Impairs Cell Proliferation in Glioblastoma.

Myeloid zinc finger 1 (MZF1), also known as zinc finger protein 42, is a zinc finger transcription factor, belonging to the Krüppel-like family that has been implicated in several types of malignancies, including glioblastoma multiforme (GBM). MZF1 is reportedly an oncogenic gene that promotes tumor progression. Moreover, higher expression of MZF1 has been associated with a worse overall survival rate among patients with GBM. Thus, MZF1 may be a promising target for therapeutic interventions. Cantharidin (CTD) has been traditionally used in Chinese medicine to induce apoptosis and inhibit cancer cell proliferation; however, the mechanism by which CTD inhibits cell proliferation remains unclear. In this study, we found that the expression of MZF1 was higher in GBM tissues than in adjacent normal tissues and low-grade gliomas. Additionally, the patient-derived GBM cells and GBM cell lines presented higher levels of MZF1 than normal human astrocytes. We demonstrated that CTD had greater anti-proliferative effects on GBM than a derivative of CTD, norcantharidin (NCTD). MZF1 expression was strongly suppressed by CTD treatment. Furthermore, MZF1 enhanced the proliferation of GBM cells and upregulated the expression of c-MYC, whereas these effects were reversed by CTD treatment. The results of our study suggest that CTD may be a promising therapeutic agent for patients with GBM and suggest a promising direction for further investigation.

Internal nitrogen and phosphorus loading in a seasonally stratified reservoir: Implications for eutrophication management of deep-water ecosystems.

Water eutrophication is a serious global issue because of excess external and internal nutrient inputs. Understanding the intensity and contribution of internal nitrogen (N) and phosphorus (P) loading in deep-water ecosystems is of great significance for water body eutrophication management. In this study, we combined intact sediment core incubation, high-resolution peeper (HR-Peeper) sampling, and analysis of N and P forms and other environmental factors in the water column and sediments to evaluate the contributions of internal N and P loading to water eutrophication by N and P fluxes across the sediment-water interface (SWI) of the Panjiakou Reservoir (PJKR), a deep-water ecosystem where eutrophication threatens the security of the local drinking water supply in North China. The results indicated that the PJKR showed obvious thermal and dissolved oxygen (DO) stratification in the warm seasons and full mixing in the cold seasons. The mean DO concentration was 9.9 and 3.55 mg/L in the epilimnion and hypolimnion, respectively, in warm seasons and 10.7 mg/L in cold seasons. The sediment acted as a source of soluble reactive phosphorus (SRP), NH4+-N, and NO2--N and a sink of NO3--N. The SRP fluxes were 5.28 ± 4.34 and 2.30 ± 1.93 mg m-2·d-1 in warm and cold seasons, respectively, and the dissolved inorganic nitrogen (DIN) fluxes were -0.66 ± 47.84 and 44.04 ± 84.05 mg m-2·d-1. Seasonal hypoxia accelerated the release of P rather than N from the sediments in warm seasons, which came mainly from Fe-P and Org-P under anoxic conditions. The strong negative NO3--N flux (diffusion from the water column to the sediment) implied an intensive denitrification process at the SWI, which can counteract the release flux of NH4+-N and NO2--N, resulting in the sediment acting as a weak dissolved inorganic nitrogen (DIN) source for the overlying water. We also found that internal N loading accounted for only ∼9% of the total N loading, while internal P loading accounted for 43% of the total P loading of the reservoir. Our results highlight that efforts to manage the internal loading of deep-water ecosystems should focus on P and seasonal hypoxia.

Patterns of internal nitrogen and phosphorus loadings in a cascade reservoir with a large water level gradient: Effects of reservoir operation and water depth.

Internal nutrient loadings pose a high risk of being an additional N and P source, exacerbating eutrophication and deteriorating water quality. In this study, we selected the Daheiting Reservoir (DHTR) in North China, with a pronounced water level gradient, to investigate internal N and P loadings, estimate N and P fluxes across the sediment‒water interface based on the pore water profiles, and reveal the potential effects of water discharge from an upstream reservoir and high-intensity cage aquaculture on the risks of internal N and P release. The results indicated that DHTR presented with severe internal nutrient loadings, and the N and P fluxes showed significant spatiotemporal variations. NH4+-N and soluble reactive phosphorus (SRP) fluxes were higher in deep areas (averages of 26.14 and 9.9 mgm-2d-1, respectively) than in shallow areas near inflows (averages of 5.0 and 1.24 mgm-2d-1, respectively). Unexpectedly, the estimated NH4+-N and SRP fluxes were the lowest in summer (averages of 3.94 and 0.33 mgm-2d-1, respectively), which may have been influenced by seasonal thermal stratification and copious discharge from the hypolimnion of the upstream reservoir (Panjiakou Reservoir). Comparison of annual internal and external N and P loadings revealed that water discharge from the upstream Panjiakou Reservoir was the dominant source of N and P to the reservoir, contributing up to 83.6% of N input and 55.4% of P input. The internal P loading also contributed to water eutrophication to a great extent, accounting for 34.7% of the total P input. Our results highlight the impact of upstream reservoir discharge operation on downstream reservoir water quality and the importance of controlling the internal nutrient loading in cascade reservoirs, and further provide theoretical and practical foundations for the development of policies and strategies to conserve reservoir ecosystems.

Patterns and drivers of CH4 concentration and diffusive flux from a temperate river-reservoir system in North China.

Freshwater reservoirs are regarded as an important anthropogenic source of methane (CH4) emissions. The temporal and spatial variability of CH4 emissions from different reservoirs results in uncertainty in the estimation of the global CH4 budget. In this study, surface water CH4 concentrations were measured and diffusive CH4 fluxes were estimated via a thin boundary layer model in a temperate river-reservoir system in North China, using spatial (33 sites) and temporal (four seasons) monitoring; the system has experienced intensive aquaculture disturbance. Our results indicated that the dissolved CH4 concentration in the reservoir ranged from 0.07 to 0.58 µmol/L, with an annual average of 0.13 ± 0.10 µmol/L, and the diffusive CH4 flux across the water-air interface ranged from 0.66 to 3.61 µmol/(m2•hr), with an annual average of 1.67 ± 0.75 µmol/(m2•hr). During the study period, the dissolved CH4 concentration was supersaturated and was a net source of atmospheric CH4. Notably, CH4 concentration and diffusive flux portrayed large temporal and spatial heterogeneity. The river inflow zone was determined to be a hotspot for CH4 emissions, and its flux was significantly higher than that of the tributary and main basin; the CH4 flux in autumn was greater than that in other seasons. We also deduced that the CH4 concentration/diffusive flux was co-regulated mainly by water temperature, water depth, and water productivity (Chla, trophic status). Our results highlight the importance of considering the spatiotemporal variability of diffusive CH4 flux from temperate reservoirs to estimate the CH4 budget at regional and global scales.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.

Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.

BACKGROUND: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. METHODS: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. RESULTS: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD. CONCLUSION: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.

Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States.

INTRODUCTION: To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA). METHODS: We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey. RESULTS: Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%). DISCUSSION: These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.

Genome-wide high-resolution mapping of DNA methylation reveals epigenetic variation in the offspring of sexual and asexual propagation in Robinia pseudoacacia.

KEY MESSAGE: We detected the genome-wide pattern of DNA methylation and its association with gene expression in sexual and asexual progenies of mature Robinia pseudoacacia trees. DNA methylation plays an important role in plant reproduction and development. Although some studies on sexual reproduction have been carried out in model plants, little is known about the dynamic changes in DNA methylation and their effect on gene expression in sexual and asexual progeny of woody plants. Here, through whole-genome bisulfite sequencing, we revealed DNA methylation patterns in the sexual and asexual progenies of mature Robinia pseudoacacia to understand the regulation of gene expression by DNA methylation in juvenile seedlings. An average of 53% CG, 34% CHG and 5% CHH contexts was methylated in the leaves of mature and juvenile individuals. The CHH methylation level of asexually propagated seedlings was significantly lower than that of seed-derived seedlings and mature trees. The intergenic regions had the highest methylation level. Analysis of differentially methylated regions (DMRs) showed that most of them were hypermethylated and located in the gene upstream and introns. A total of 24, 108 and 162 differentially expressed genes containing DMRs were identified in root sprouts (RSs), root cuttings (RCs) and seed-derived seedlings (SSs), respectively, and a large proportion of them showed hypermethylation. In addition, DMRs were enriched within GO subcategories including catalytic activity, metabolic process and cellular process. The results reveal widespread DNA methylation changes between mature plants and their progenies through sexual/asexual reproduction, which provides novel insights into DNA methylation reprogramming and the regulation of gene expression in woody plants.