Background
Cancer is one of the leading causes of death and a main economic burden in China. Investigating the differences in cancer patterns and control strategies between China and developed ...countries could provide reference for policy planning and contribute to improving cancer control measures. In this study, we reviewed the rates and trends of cancer incidence and mortality and disability‐adjusted life year (DALY) burden in China, and compared them with those in the United States (US) and the United Kingdom (UK).
Methods
Cancer incidence, mortality, and DALY data for China, US and UK were obtained from the GLOBOCAN 2020 online database, Global Burden of Disease (GBD) 2019 study, and Cancer Incidence in Five Continents plus database (CI5 plus). Trends of cancer incidence and mortality in China, US, and UK were analyzed using Joinpoint regression models to calculate annual percent changes (APCs) and identify the best‐fitting joinpoints.
Results
An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020. Additionally, cancers resulted in 67,340,309 DALYs in China. Compared to the US and UK, China had lower cancer incidence but higher cancer mortality and DALY rates. Furthermore, the cancer spectrum of China was changing, with a rapid increase incidence and burden of lung, breast, colorectal, and prostate cancer in addition to a high incidence and heavy burden of liver, stomach, esophageal, and cervical cancer.
Conclusions
The cancer spectrum of China is changing from a developing country to a developed country. Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China. Therefore, the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well‐established in the developed countries, and taking consideration of the diversity of cancer types by of different regions in China at the same time.
The cancer spectrum of China is changing, with a rapidly increase incidence and burden of "cancers of the rich" (lung, breast, colorectal, and prostate cancer) in addition to a high incidence and heavy burden of “cancers of the poor” (liver, stomach, esophageal, and cervical cancer).
Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarker in many cancers. Here, we conducted a study to investigate the potential use of ctDNA methylation markers for ...the diagnosis and prognostication of colorectal cancer (CRC) and used a prospective cohort to validate their effectiveness in screening patients at high risk of CRC. We first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. Then, we applied a machine learning algorithm to develop a predictive diagnostic and a prognostic model using cell-free DNA (cfDNA) samples from a cohort of 801 patients with CRC and 1021 normal controls. The obtained diagnostic prediction model discriminated patients with CRC from normal controls with high accuracy (area under curve = 0.96). The prognostic prediction model also effectively predicted the prognosis and survival of patients with CRC (
< 0.001). In addition, we generated a ctDNA-based molecular classification of CRC using an unsupervised clustering method and obtained two subgroups of patients with CRC with significantly different overall survival (
= 0.011 in validation cohort). Last, we found that a single ctDNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a high-risk population of 1493 participants in a prospective cohort study. Together, our findings showed the value of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of CRC.
Early embryonic exogenous feeding of bioactive substances is a topic of interest in poultry production, potentially improving gastrointestinal tract (GIT) development, stimulating immunization, and ...maximizing the protection capability of newly hatched chicks. However, the biophysiological actions and effects of in ovo administered bioactive substances are inconsistent or not fully understood. Thus, this paper summarizes the functional effects of bioactive substances and their interaction merits to augment GIT development, the immune system, and microbial homeostasis in newly hatched chicks. Prebiotics, probiotics, and synbiotics are potential bioactive substances that have been administered in embryonic eggs. Their biological effects are enhanced by a variety of mechanisms, including the production of antimicrobial peptides and antibiotic responses, regulation of T lymphocyte numbers and immune-related genes in either up- or downregulation fashion, and enhancement of macrophage phagocytic capacity. These actions occur directly through the interaction with immune cell receptors, stimulation of endocytosis, and phagocytosis. The underlying mechanisms of bioactive substance activity are multifaceted, enhancing GIT development, and improving both the innate and adaptive immune systems. Thus summarizing these modes of action of prebiotics, probiotics and synbiotics can result in more informed decisions and also provides baseline for further research.
Nasopharyngeal cancer (NPC) is one of the most common head and neck cancers.
This study describes the global epidemiological profiles of NPC incidence and mortality in 185 countries in 2020 and the ...projected burden in 2040.
The estimated numbers of NPC cases and deaths were retrieved from the GLOBOCAN 2020 data set. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were calculated using the world standard. The future number of NPC cases and deaths by 2040 were estimated based on global demographic projections.
Globally, approximately 133,354 cases and 80,008 deaths from NPC were estimated in 2020 corresponding to ASIRs and ASMRs of 1.5 and 0.9 per 100,000 person-years, respectively. The largest numbers of both global cases and deaths from NPC occurred in Eastern Asia (65,866/133,354, 49.39% and 36,453/80,008, 45.56%, respectively), in which China contributed most to this burden (62,444/133,354, 46.82% and 34,810/80,008, 43.50%, respectively). The ASIRs and ASMRs in men were approximately 3-fold higher than those in women. Incidence rates varied across world regions, with the highest ASIRs for both men and women detected in South-Eastern Asia (7.7 and 2.5 per 100,000 person-years, respectively) and Eastern Asia (3.9 and 1.5 per 100,000 person-years, respectively). The highest ASMRs for both men and women were found in South-Eastern Asia (5.4 and 1.5 per 100,000 person-years, respectively). By 2040, the annual number of cases and deaths will increase to 179,476 (46,122/133,354, a 34.58% increase from the year 2020) and 113,851 (33,843/80,008, a 42.29% increase), respectively.
Disparities in NPC incidence and mortality persist worldwide. Our study highlights the urgent need to develop and accelerate NPC control initiatives to tackle the NPC burden in certain regions and countries (eg, South-Eastern Asia, China).
Nasopharyngeal carcinoma is an Epstein–Barr Virus (EBV) associated malignancy which is highly prevalent in Southeast Asia. EBV‐related antibodies have been widely used as screening markers for early ...nasopharyngeal carcinoma (NPC) detection. However, due to its low positive predictive rate, it is essential to develop new biomarkers to facilitate NPC early diagnosis or triage EBV serological high‐risk individuals to improve the chance of NPC early detection. BART microRNAs, which are encoded by BamHI region of EBV, were reported to be abundant in NPC and have potential value in early diagnosis of NPC. Here, we quantified circulating level of 17 BART microRNAs in discovery stage based on previous microarray and sequencing data and, in particular, BART 2‐5p, the sole candidate whose area under curve (AUC) was higher than 0.8, has been chosen for further study. In validation stage, the sensitivity, specificity and AUC of BART 2‐5p was 93.9%, 89.8%, 0.972 (95%CI: 0.954–0.989), respectively, in Cohort 1 constituted by NPC patients and controls from Hong Kong. For validation Cohort 2 consisting of patients and controls from Guangzhou, the sensitivity, specificity and AUC was 94.2%, 83.5%, 0.959 (95%CI: 0.939–0.980), respectively. To evaluate its ability to distinguish preclinical NPC patients, we established a nested case–control study with serum samples prospectively collected from 22 NPC patients prior to their clinical diagnosis and 88 matched healthy high‐risk controls in a screening trial. The sensitivity and specificity were 90.9% and 54.5%. Collectively, EBV microRNA BART2‐5p may be a valuable biomarker for early detection of NPC.
What's new?
Nasopharyngeal carcinoma (NPC) is a malignancy related to Epstein–Barr Virus (EBV) infection, and early diagnostic markers are urgently needed given the high prevalence of the cancer in Southeast Asia and South China. Here the authors evaluated BART micro‐RNAs, a cluster of 40 mature micro‐RNAs encoded by EBV, as early diagnostic markers. They find that BART 2‐5p could successfully distinguish NPC patients from controls, and serum levels were increased even before clinical diagnosis of NPC, underscoring its potential as early diagnostic marker.
Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal ...carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial–mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients’ survival.
An experiment was conducted to investigate the effect of organic and inorganic Fe sources on Fe absorption and expression of related transporters in the small intestine of broilers. Iron-deficient ...intact broilers (7-day-old) were fed an Fe-unsupplemented corn-soybean meal basal diet or the basal diet supplemented with 60 mg Fe/kg as Fe sulfate (FeSO4•7H2O), Fe-Met with weak chelation strength (Fe-Met W), Fe-proteinate with moderate chelation strength (Fe-Prot M) or Fe-proteinate with extremely strong chelation strength (Fe-Prot ES) for 14 d. The plasma Fe contents were enhanced (P < 0.02) by Fe addition, and greater (P < 0.0002) in Fe-Prot M and Fe-Prot ES groups than in Fe-Met W and FeSO4 groups. Supplemental Fe decreased (P < 0.03) the divalent metal transporter 1 (DMT1) mRNA levels in the duodenum and jejunum, and ferroportin 1 (FPN1) mRNA levels in the duodenum on d 21, but no differences (P > 0.20) were detected among different Fe sources. Regardless of Fe source, the mRNA levels of DMT1 and FPN1 were higher (P < 0.02) in the duodenum than in the jejunum and ileum, and in the jejunum than in the ileum (P < 0.05). However, Fe addition did not affect (P > 0.10) the mRNA levels of amino acid transporters and protein levels of DMT1 and FPN1 in the small intestine of broilers. These results indicate that organic Fe sources with stronger chelation strength showed higher Fe absorption in broilers in vivo; the mRNA expression of Fe and amino acid transporters varied along with the extension of the small intestine; the absorption of Fe as organic Fe chelates was not mediated by the amino acid transporters in intact chicks in this study.
Adiponectin is an adipocyte-secreted cytokine that enhances insulin sensitivity and attenuates inflammation. Although circulating adiponectin level is often inversely associated with several ...malignancies, its role in the development of nasopharyngeal carcinoma (NPC) remains unclear. Here, we investigated the clinical association between circulating adiponectin level and NPC, and examined the impact of adiponectin, as well as the underlying mechanisms, on NPC growth both in vitro and in vivo.
The association between circulating adiponectin level and the risk of developing NPC was assessed in two different cohorts, including a hospital-based case-control study with 152 cases and 132 controls, and a nested case-control study with 71 cases and 142 controls within a community-based NPC screening cohort. Tumor xenograft model, cell proliferation and cycle assays were applied to confirm the effects of adiponectin on NPC growth in cultured cells and in xenograft models. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis.
High adiponectin levels were associated with a monotonic decreased trend of NPC risk among males in both the hospital-based case-control study and a nested case-control study. In vitro, recombinant human full-length adiponectin significantly inhibited NPC cell growth and arrested cell cycle, which were dependent on AMPK signaling pathway. The growth of xenograft of NPC tumor was sharply accelerated in the nude mice carrying genetic adiponectin deficiency. An adiponectin receptor agonist, AdipoRon, displayed strong anti-tumor activity in human xenograft models.
These findings demonstrated for the first time that circulating adiponectin is not only inversely associated with NPC, but also controls the development of NPC via AMPK signaling pathway. Stimulation of adiponectin function may become a novel therapeutic modality for NPC.
A two‐stage study was conducted in southern China to determine and validate an optimal combination of Epstein‐Barr virus (EBV)‐related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the ...first stage, six seromarkers VCA‐IgA, EA‐IgA, Epstein‐Barr virus nuclear antigen 1 (EBNA1‐IgA), EBNA1‐IgG, Zta‐IgA and Rta‐IgG were detected by enzyme‐linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA‐IgA and EA‐IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA‐IgA and EA‐IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA‐IgA combined with EBNA1‐IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30–59 years and without clinical evidence of NPC were recruited into a population‐based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA‐IgA and EBNA1‐IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high‐incidence areas.
Abstract
Background
Phosphorus is essential for bone mineralization in broilers, however, the underlying mechanisms remain unclear. We aimed to investigate whether bone phosphorus retention and bone ...development might be regulated by related hormones and local bone-derived regulators in broilers.
Methods
Broilers were fed diets containing different levels of non-phytate phosphorus (NPP) 0.15%, 0.25%, 0.35%, 0.45% and 0.55% or 0.15%, 0.22%, 0.29%, 0.36% and 0.43% from 1 to 21 or 22 to 42 days of age. Serum and tibia samples were collected for determinations of bone phosphorus retention and bone development parameters, related hormones and local bone-derived regulators of broiler chickens on d 14, 28 and 42, respectively.
Results
Tibia ash phosphorus, total phosphorus accumulation in tibia ash (TP
TA
), bone mineral concentration (BMC), bone mineral density (BMD), bone breaking strength (BBS), and ash on d 14, 28 or 42, serum 1,25-dihydroxyvitamin D
3
(1,25(OH)
2
D
3
) on d 28 and 42, mRNA expressions of tibia fibroblast growth factor 23 (
FGF23
) and dentin matrix protein 1 (
DMP1
) on d 14 and 28 increased linearly or quadratically (
P
< 0.05), while serum parathyroid hormone (PTH) on d 28, tibia alkaline phosphatase (ALP) on d 14, 28 and 42, bone gal protein (BGP) on d 14, and mRNA expression of tibia phosphate-regulating gene with homologies to endopeptidases on the X chromosome (
PHEX
) on d 14 and 28 decreased linearly or quadratically (
P
< 0.04) as dietary NPP level increased. TP
TA,
BMC, BMD, and ash on d 28 and 42, BBS on d 28, and ash phosphorus on d 42 were positively correlated (
r
= 0.389 to 0.486,
P <
0.03) with serum 1,25(OH)
2
D
3
. All of the above parameters were positively correlated (
r
= 0.380 to 0.689,
P <
0.05) with tibia
DMP1
mRNA expression on d 14, 28 and 42, but negatively correlated (
r
= − 0.609 to − 0.538,
P <
0.02) with serum PTH on d 28, tibia ALP on d 14, 28 and 42, and BGP on d 14. TP
TA
, BMC and ash on d 14 and BMD on d 28 were negatively correlated (
r
= − 0.397 to − 0.362,
P <
0.03) with tibia
PHEX
mRNA expression, and BMD on d 28 was positively correlated (
r
= 0.384,
P =
0.04) with tibia
FGF23
mRNA expression.
Conclusions
These results suggested that bone phosphorus retention and bone development parameters had moderate to strong correlations with serum PTH and 1,25(OH)
2
D
3
and tibia DMP1, PHEX, FGF23, ALP and BGP in broilers during the whole growth period, and thus they might be partly regulated by these related hormones and local bone-derived regulators.
PDF
