Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma.

BACKGROUND: CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned. RESULTS: We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model. CONCLUSIONS: Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.

Baseline Performance of Ultrasound-Based Strategies in Breast Cancer Screening Among Chinese Women.

RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3‰) in the 35-44 years age group and 25 (4.2‰) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.

Knowledge, attitude, and perception towards COVID-19 vaccinations among the adults in Rwanda: a cross-sectional study.

BACKGROUND: Multiple vaccinations have received approval for the prevention of the coronavirus illness. Nevertheless, the sluggish vaccination rate is mostly attributed to the general population's limited understanding and unwillingness to accept the use of vaccinations. Thus, it is important to investigate the Rwandan population's knowledge, attitudes, and perceptions toward COVID-19 vaccines. METHODS: A cross-sectional survey was conducted among 370 participants from 11th to 17th February 2023. Demographic information was gathered, and knowledge, attitudes, and perceptions of COVID-19 vaccinations were assessed. A binary logistic regression analysis was undertaken to determine the parameters that determine the perception of COVID-19 vaccinations. RESULTS: This study included 370 participants. Among them, 85% had good knowledge about COVID-19 vaccines, and 84% had a positive attitude towards them. Additionally, the study had a diverse group, with half of the participants being female and nearly half falling between the ages of 30 and 39. Several key findings emerged through logistic regression analysis. Those aged 30-39 had 1.39 times higher odds of positive perception than 18-28 (OR = 1.39, 95% CI = 1.08-3.24). Participants with a university education were twice as likely to have a positive perception compared to those without an education level (OR = 2.43, 95% CI = 1.30-6.20). Additionally, single individuals were three times more likely to have a positive perception than their married counterparts (OR = 3.39, 95% CI = 1.28-9.09). Vaccinated individuals had twice the odds of positive perception than non-vaccinated individuals (OR = 2.89, 95% CI = 1.01-8.89). Those receiving information from government health institutions were three times more likely to have a positive perception than those who received the information from friends (OR = 3.19, 95% CI = 1.02-12.7). Moreover, employed participants were four times more likely to have a positive perception non-employed individuals (OR = 4.21, 95% CI = 1.48-13.6). Besides, gender and COVID-19 diagnosis did not significantly correlate with positive COVID-19 vaccine perception. CONCLUSION: The results indicate that the general public in Rwanda has good knowledge, positive attitudes, and a positive perception toward the COVID-19 vaccination, however, some of the participants had some misconceptions towards COVID-19. The findings of this study will be valuable for policymakers and healthcare authorities working to improve vaccination rates.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

An integrated data analysis reveals distribution, hosts, and pathogen diversity of Haemaphysalis concinna.

BACKGROUND: Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens. METHODS: A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling. RESULTS: Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa. CONCLUSIONS: Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced.

Virome diversity shaped by genetic evolution and ecological landscape of Haemaphysalis longicornis.

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.

Epidemiological behaviour and interventions of malaria in Niger, 2010-2019: a time-series analysis of national surveillance data.

BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Systematic review and integrated data analysis reveal diverse pangolin-associated microbes with infection potential.

There has been increasing global concern about the spillover transmission of pangolin-associated microbes. To assess the risk of these microbes for emergence as human pathogens, we integrated data from multiple sources to describe the distribution and spectrum of microbes harbored by pangolins. Wild and trafficked pangolins have been mainly recorded in Asia and Africa, while captive pangolins have been reported in European and North American countries. A total of 128 microbes, including 92 viruses, 25 bacteria, eight protists, and three uncharacterized microbes, have been identified in five pangolin species. Out of 128 pangolin-associated microbes, 31 (including 13 viruses, 15 bacteria, and three protists) have been reported in humans, and 54 are animal-associated viruses. The phylogenetic analysis of human-associated viruses carried by pangolins reveals that they are genetically close to those naturally circulating among human populations in the world. Pangolins harbor diverse microbes, many of which have been previously reported in humans and animals. Abundant viruses initially detected in pangolins might exhibit risks for spillover transmission.

Epidemiological and phylogenetic characteristics of emerging Anaplasma capra: A systematic review with modeling analysis.

Anaplasma capra, an emerging tick-borne pathogen, has caused a lot of concern since initially recognized in goats and patients in China in 2015, and has been reported in a wide range of domestic and wild animals as well as ticks worldwide, posing a threat to public health. In this systematic review, we established a comprehensive database to acquire the distribution and prevalence status of this pathogen, and collected all sequences of A. capra to summarize the details of genetic diversity by phylogenetic analysis. We also predicted the possible global distribution of A. capra by using ecological niche model. A. capra has been known to distribute in 18 countries across Asia, Europe and Africa. A total of 19 species of mammals from seven families have been reported as hosts, and domestic ruminants including goats, sheep and cattle were the major hosts. At least 8 tick species of 4 genera have been reported to carry A. capra, and Haemaphysalis longicornis was most commonly infected. Sheep and Rhipicephalus microplus had the highest positive rates among animals and ticks. Phylogenetic analysis based on gltA and groEL genes revealed that A. capra could primarily be divided into two clusters related to geographic location and animal hosts. The predictive model showed that the most suitable habitats for presence of A. capra were mainly located in Asia and eastern Europe. These cumulative data regarding A. capra of our study lay a foundation for the subsequent exploration of this emerging tick-borne pathogen.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

A novel recessive mutation in OXR1 is identified in patient with hearing loss recapitulated by the knockdown zebrafish.

Hereditary hearing loss is a highly genetically heterogeneous disorder. More than 150 genes have been identified to link to human non-syndromic hearing impairment. To identify genetic mutations and underlying molecular mechanisms in affected individuals and families with congenital hearing loss, we recruited a cohort of 389 affected individuals in 354 families for whole-exome sequencing analysis. In this study, we report a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in the OXR1 gene, which was identified in a 4-year-old girl with sensorineural hearing loss. OXR1 encodes Oxidation Resistance 1 and is evolutionarily conserved from zebrafish to human. We found that the ortholog oxr1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL) in zebrafish. Knockdown of oxr1b in zebrafish resulted in a significant developmental defect of SAG and pLL. This phenotype can be rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs. OXR1-associated pathway analysis revealed that mutations of TBC1D24, a TLDc-domain-containing homolog gene of OXR1, have previously been identified in patients with hearing loss. Interestingly, mutations or knockout of OXR1 interacting molecules such as ATP6V1B1 and ESR1 are also associated with hearing loss in patients or animal models, hinting an important role of OXR1 and associated partners in cochlear development and hearing function.

Somatic embryogenesis of Arabica coffee in temporary immersion culture: Advances, limitations, and perspectives for mass propagation of selected genotypes.

Culture in temporary immersion systems (TIS) is a valuable tool for the semi-automation of high frequency somatic embryogenesis of coffee. This system allows the intermittent exposure of explants to liquid medium in cycles of specific frequency and duration of immersion with renewal of the culture atmosphere in each cycle. TIS have revolutionized somatic embryogenesis of coffee plants as an alternative for scaling up and reducing costs associated with labor-intensive solid media culture. In Central America, somatic embryogenesis is employed on a commercial scale to produce F1 Coffea arabica hybrids. In Asia and Africa, somatic embryogenesis is used for the multiplication of selected genotypes of C. arabica and C.canephora. Somatic embryogenesis of coffee plants is considered a model system for woody species due to its biological versatility and low frequency of somaclonal variation. Nevertheless, the success of somatic embryogenesis for mass propagation of coffee plants depends on the development, optimization, and transfer of complementary technologies. Temporary immersion using the RITA® bioreactor is, so far, the best complementary tool for somatic embryogenesis of Arabica coffee for a single recipient with simple changes in liquid media. Likewise, high volume bioreactors, such as 10-L glass BIT® and 10-L flexible disposable plastic bags, have been successfully used for somatic embryogenesis of other coffee species. These bioreactors allow the manipulation of thousands of embryos under semi-automated conditions. The protocols, advantages, and benefits of this technology have been well documented for organogenesis and somatic embryogenesis pathways. However, adaptation in commercial laboratories requires technical and logistical adjustments based on the biological response of the cultures as well as the costs of implementation and production. This review presents the historical and present background of TIS and its commercial application and, in particular, pertinent information regarding temporary immersion culture for C. arabica somatic embryogenesis. The main limitations of this technology, such as hyperhydricity, asynchrony, and developmental abnormalities, are examined, and a critical analysis of current knowledge regarding physiological, biochemical, and molecular aspects of the plant response to temporary immersion is offered. Further, perspectives are provided for understanding and solving the morpho-physiological problems associated with temporary immersion culture of coffee plants. Systematic Review Registration.

Incidence and mortality of lung cancer in 2018 and the temporal trends from 2010 to 2018 in Henan province, China: a population-based registry study.

Background: The disease burden of lung cancer is high in Henan province, China, it is out of the utmost significance to figure the current epidemic status and temporal trend of lung cancer for effective prevention and control. Methods: The qualified data was obtained from the Henan Provincial Central Cancer Registry of China, covering 30.51% of the whole population. Incidence, mortality, proportions, and cumulative rates (among patients aged 0-74 years old) of lung cancer by areas, sex and age groups were estimated. The world Segi's standard population was applied to calculate the age-standardized rate. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate temporal trends from 2010 to 2018. Results: In 2018, there were about 55,344 new cases of lung cancer in Henan province, with the crude incidence of 50.75/100,000, the age-standardized incidence rate by world standard (Segi's) population (ASIRW) of 37.14/100,000, and the cumulative rate of 4.57%. About 41,782 people died from lung cancer in 2018, with the crude mortality rate of 38.31/100,000, the age-standardized mortality rate by world standard (Segi's) population (ASMRW) of 27.09/100,000, and the cumulative rate of 3.22%. The age-specific incidence and mortality of lung cancer increased gradually as age increased and reached the peak at the age of 85+ years. The overall ASIRW (AAPC =0.3, P=0.531) and ASMRW (AAPC =-0.2, P=0.687) remained stable from 2010 to 2018, but decreased in urban areas from 2014 to 2018 (APC for ASIRW =-4.7, P=0.023; APC for ASMRW =-5.3, P=0.012). From 2010 to 2018, the incidence rate increased in the rural population aged 75+ years old (AAPC =4.2, P=0.023). Conclusions: The incidence and mortality rates of lung cancer significantly decreased in urban areas partly due to the Cancer Screening Program in Urban China. Nonetheless, the disease burden remains high, especially in males and elderly population. Comprehensive prevention and control programs, such as smoking cessation intervention, screening, early diagnosis and early treatment programs, need to be implemented to reduce the burden of lung cancer.

A cluster randomized controlled trial to evaluate the efficacy of esophageal and gastric cancer screening in mortality reduction in a non-high-incidence area: methodology and initial results.

Background: A cluster randomized controlled trial of endoscopy-based screening for esophageal cancer (EC) and gastric cancer (GC) was conducted to evaluate the efficacy and feasibility of this strategy in a non-high-incidence rural area of China. The trial design and baseline findings are presented here. Methods: A total of 33 eligible villages in Luoshan County in Henan Province were assigned randomly to the intervention or control group in a 1:1 ratio by a computer-generated randomization list. Local residents aged 40 to 69 years were enrolled from the villages. Participants in the intervention group were risk-stratified with a questionnaire, and high-risk individuals were subsequently screened by endoscopy. The primary outcomes were EC and GC mortality. The secondary outcomes comprised the detection rate, stage distribution, and the treatment rate. In this study, baseline characteristics were assessed by a questionnaire. Multivariate logistic regression analysis was performed to explore factors associated with endoscopy compliance. Results: Trial recruitment was completed in 2017, and ultimately, there were 12,475 and 11,442 participants allocated to the intervention (17 clusters) and the control group (16 clusters), respectively. We included 23,653 participants in the analysis, with 12,402 in the intervention group and 11,251 in the control group. A total of 6,286 (50.7%) participants in the intervention group were estimated as high-risk individuals, and 2,719 (43.3%) underwent endoscopy. Multivariate logistic regression analysis demonstrated that some factors including age, gender, education, personality and mental health, and upper gastrointestinal diseases or symptoms might affect endoscopy compliance. The detection rates for positive cases of EC and GC were 0.22% and 0.55%, respectively. The rates for esophageal and gastric precancerous lesions were 0.70% and 2.35%, respectively. The early detection rates for EC and GC were 50.0% and 33.3%, respectively. Additionally, the overall treatment rate for positive cases was 90.0%. Conclusions: The diagnostic yield of endoscopy-based screening for EC and GC was relatively low in a non-high-incidence rural area. The study may offer clues for the improvement of endoscopy compliance and the optimization of screening strategies for upper gastrointestinal cancer in non-high-incidence areas. Trial Registration: Chinese Clinical Trial Registry ChiCTR-EOR-16008577.

Incidence and mortality of colorectal cancer in 2017 and the time-trend from 2010 to 2017 in Henan province, China: a population-based registry study.

Background: Henan province is an area with a serious disease burden of colorectal cancer (CRC) in China. Understanding the current incidence and mortality and the time-trend is critical to formulate and optimize prevention and control strategies for CRC. However, the current incidence and mortality and time-trend of CRC in Henan province, China have not been reported. Methods: CRC data was got from the Henan Provincial Central Cancer Registry of China in which the data was submitted from local cancer registries. Combined with the census data, the incidence, mortality, proportion, age-standardized rate by Chinese population (ASRC), age-standardized rate by world population (ASRW), and cumulative incidence and mortality (0-74 years old) of CRC by urban and rural population, gender, and age groups were estimated. The average annual percentage change (AAPC) and its 95% confidence interval (CI) of ASRC from 2010 to 2017 were analyzed. Results: In 2017, it was estimated that there were 20,275 new cases and 10,046 deaths of CRC in Henan province. The crude incidence was 18.73/100,000, with an age-standardized incidence rate by Chinese population (ASIRC) of 13.97/100,000 and age-standardized mortality rate by world population (ASIRW) of 13.78/100,000. The cumulative incidence was 1.66%. The mortality rate was 9.28/100,000, with an age-standardized mortality rate by Chinese population (ASMRC) of 6.49/100,000 and an age-standardized mortality rate by world population (ASMRW) of 6.45/100,000. The cumulative mortality rate was 0.69%. The ASIRC and ASMRC were higher in urban areas (15.89/100,000, 7.19/100,000) than in rural areas (13.13/100,000, 6.20/100,000), and higher in males (15.53/100,000, 7.44/100,000) than in females (12.48/100,000, 5.66/100,000). The age-specific incidence reached the peak at age of 80-84, and the age-specific mortality reached the peak at age 85. From 2010 to 2017, the overall ASIRC and ASMRC showed a steady trend (P>0.05), while an upward trend was observed in the mortality rate in urban males (AAPC =3.4, 95% CI: 0.2-6.7, P=0.040). Conclusions: The incidence and mortality of CRC were high in Henan province, and higher in urban areas and males. It is critical to strengthen the prevention and control of CRC, carry out targeted intervention, and promote screening and early diagnosis and treatment, particularly among urban areas and males.

Time-trend of the incidence and mortality of esophageal cancer from 2010 to 2018 and its statistics in 2018 in Henan, China.

Background: It is great of significance to figure the time-trend of esophageal cancer (EC) and its current status for effective prevention and control, especially in EC high risk areas. As one of world-renowned high-risk areas, the epidemiology of EC in Henan has not been recently updated. Therefore, we aimed to depict the status quo of EC and analyze its time-trend in Henan. Methods: The EC data were extracted from the Henan Provincial Cancer registry database derived from the population based cancer registry system, which covered 30.51% of the whole population in Henan and were qualified according to national and international guidelines. The incidence and mortality of EC were estimated by area (rural/urban), gender, and age groups. The age-standardized rates (ASRs) were calculated according to the Segi's population. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate the time-trend of EC. Results: As estimated, there were 29,913 new EC cases in Henan, 2018. The crude incidence and the age-standardized incidence rate by world standard population (ASIRW) was 27.43/105 and 19.96/105, respectively. The incidence in males and rural was 1.83 and 1.51 times higher than that in females and urban areas, respectively. Meanwhile, it was estimated that 22,688 deaths occurred in 2018. The crude mortality and the age-standardized mortality rate by world standard population (ASMRW) were 20.80/105 and 14.47/105, respectively. Similarly, males and rural areas had higher mortality compared with females and urban areas. The age-specific incidence and mortality of EC showed significant increasing after 60-64 years group. In general, the time-trend of incidence (APC: -8.9, P<0.001) and mortality (APC: -7.6, P<0.001) of EC showed a significant decreasing trend since 2014, and downward trend were also observed in rural areas for incidence (APC: -5.2, P<0.001) and mortality (APC: -3.9, P<0.001) from 2010 to 2018. Conclusions: The EC incidence and mortality in Henan has exhibited a significant declining trend in past years. Nonetheless, the disease burden remains high, especially in males and rural areas. Therefore, the ongoing prevention and control strategies of EC should be maintained alongside the establishment of more effective strategies.

Status and associated factors of cross-regional healthcare-seeking among patients with advanced colorectal cancer in China: a multicenter cross-sectional study.

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services. Methods: From March 2020 to March 2021, a cross­sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4. Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care. Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services.

The choice of medical facility and associated factors among Chinese advanced colorectal cancer patients: a cross-sectional multi-center study.

Background: Colorectal cancer (CRC) poses a significant public health burden worldwide. The investigation of the choice of medical facility among CRC patients is helpful for understanding access to health services and improving quality of oncology services to optimize health outcomes. However, there are limited studies on the topic. The objective of this study was to investigate the choice of medical facility and its associated factors among advanced CRC patients. Methods: This cross-sectional multi-center study included a total of 4,589 individuals with advanced CRC from 19 hospitals in 7 geographic regions in China. Participants were recruited by multi-stage stratified sampling. In the first stage, two cities in each geographic region were selected through simple random sampling. In the second stage, one tertiary cancer hospital and/or one general hospital were selected in each city. Data on medical experience and demographics were collected via a questionnaire during face-to-face interviews. Explanatory variables were selected based on the Andersen behavioral model. Multinomial logistic regression analyses were performed to explore the factors associated with the level of medical facility for the first treatment. Results: Hospitals at the prefecture level were the most common medical facility sought by advanced CRC patients for initial medical care (44.9%), the first definite diagnosis (46.3%), the first treatment (39.5%), and regular follow-up (38.9%). However, the first priority was changed to hospitals at the national level for the second treatment (38.0%) and after recurrence and metastasis (45.9%). Female {odds ratios (ORs) ranged from 1.31 [95% confidence interval (CI): 1.01-1.71] to 1.41 (95% CI: 1.07-1.87)} and relatively well-educated individuals [ORs ranged from 1.74 (95% CI: 1.20-2.53) to 7.26 (95% CI: 4.18-12.60)] preferred to seek higher-level health facilities. Individuals with metastatic CRC at diagnosis were more likely to visit hospitals in provincial capitals versus hospitals at the county level (OR =1.68, 95% CI: 1.27-2.22). Individuals with "good" health-related quality of life (HRQOL) (OR =0.63, 95% CI: 0.49-0.81) were less likely to seek hospitals at the prefecture level compared with hospitals at the county level. Conclusions: There is a need to improve the oncology services for CRC patients, including the optimization of referral reform policy and the promotion of quality of primary healthcare service. The results may provide evidence to fill the policy-implementation gap and potentially contribute to the improvement of the efficiency of the healthcare system.

The De Novo Genome Sequencing of Silver Pheasant (Lophura nycthemera).

Silver pheasant (Lophura nycthemera) belongs to Phasianidae, Galliformes, which exhibits high subspecific differentiation. In this study, we assembled a novel genome based on 98.42 Gb of Illumina sequencing data and 30.20 Gb of PacBio sequencing data. The size of the final assembled genome was 1.01 Gb, with a contig N50 of 6.96 Mb. Illumina paired-end reads (94.96%) were remapped to the contigs. The assemble genome shows high completeness, with a complete BUSCO score of 92.35% using the avian data set. A total of 16,747 genes were predicted from the generated assembly, and 16,486 (98.44%) of the genes were annotated. The average length of genes, exons, and introns were 19,827.53, 233.69, and 1841.19 bp, respectively. Noncoding RNAs included 208 miRNAs, 40 rRNAs, and 264 tRNAs, and a total of 189 pseudogenes were identified; 116.31 Mb (11.47%) of the genome consisted of repeat sequences, with the greatest proportion of LINEs. This assembled genome provides a valuable reference genome for further studies on the evolutionary history and conversion genetics of L. nycthemera and the phylogenomics of the Galliformes lineage.

Lupus susceptibility region containing CTLA4 rs17268364 functionally reduces CTLA4 expression by binding EWSR1 and correlates IFN-α signature.

BACKGROUND: Dysregulation of T cells mediated immune responses is a hallmark in the development of systemic lupus erythematosus (SLE). Recent genome wide association study (GWAS) revealed the genetic contribution of variants located in the cytotoxic T lymphocyte-associated protein-4 (CTLA4)-inducible T cell co-stimulator (ICOS) intergenic region to SLE susceptibility. Our aim is to find a functional variant in this region. METHODS: The genetic association results in the CTLA4-ICOS region from previous GWAS were adopted to select the potential variant which was further replicated in two independent cohorts (Henan cohort 2053 SLE patients and 1845 healthy controls, Beijing cohort 2303 SLE patients and 19,262 healthy). In order to explore the functional significance in SLE, bioinformatics with validation experiments (including electrophoretic mobility shift assay and luciferase reporter assay) and mRNA expression analysis were also performed. RESULTS: A variant located in the CTLA4-ICOS intergenic region, rs17268364, was associated with susceptibility to SLE patients in Chinese populations (risk allele, pmeta = 7.02×10-11, OR 1.19, 95%CI 1.13-1.26). The bioinformatics suggested that rs17268364 might affect the expression of CTLA4, not ICOS. The rs17268364 risk G allele containing sequence reduced the expression of the reporter gene by binding transcriptional repressor Ewing sarcoma breakpoint region 1 (EWSR1). Following genotype-mRNA expression, the analysis also showed the risk allele of rs17268364 was associated with low CTLA4 expression in lupus nephritis (LN) patients. Healthy individuals carrying rs17268364 risk G allele was significantly correlated with higher levels of IFN-α signature including increased lymphocyte antigen 6E (LY6E) (p=0.031), interferon-stimulated gene 15 (ISG15) (p=0.038), interferon regulatory factor 9 (IRF9) (p=0.028), and interferon regulatory factor 5 (IRF5) (p=0.040) mRNA expression. CONCLUSIONS: The present study confirmed the functional role of rs17268364 in the CTLA4-ICOS intergenic region that increased SLE susceptibility in the Chinese population.