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Yang, X.

Publications and source records attributed to Yang, X..

At least 883 records · Page 49Linked to original sources

A new method of teaching medical statistics at medical universities in Guangdong

Although statistics play a significant role in the medical profession, studying medical statistics is challenging because this topic is more difficult to comprehend than other subjects included in medical curricula. Therefore, improving the teaching of medical statistics to meet the requirements of modern medical students/physicians is an essential task. In this study, based on responses about studying medical statistics completed by medical students, we developed a novel approach to teaching medical statistics named "purpose, database, types of variable, and relationship between variables (PDTR)", which emphasizes how to simply master statistical applications and reduces class hours for students. Also, pilot course was implemented. We discovered that the participants using PDTR performed better on examinations of medical statistics than did graduates of institutions using traditional teaching methods (86.39{+/-}3.72 vs 73.72{+/-}6.58, P < 0.001). In addition, positive feedback was received by participants (>80%). Altogether, as a completely novel pedagogical method of teaching medical statistics, PDTR overcomes the negative attitudes of students towards medical statistics, enhances enthusiasm for learning statistics, and remarkably simplifies the process of studying statistical applications. These advantages are undoubtedly conductive to improving the effective use of medical statistics in physicians professional work.

scientific communication and education↗

DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging

There are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, aging is associated with a loss of epigenetic information that occurs in response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable epigenetic changes with age, including alterations to DNA methylation patterns that serve as epigenetic \"age\" clocks, but what drives these changes is not known. Using a transgenic mouse system called \"ICE\" (for inducible changes to the epigenome), we show that a tissues response to non-mutagenic DSBs reorganizes the epigenome and accelerates physiological, cognitive, and molecular changes normally seen in older mice, including advancement of the epigenetic clock. These findings implicate DSB-induced epigenetic drift as a conserved cause of aging from yeast to mammals.\n\nOne Sentence SummaryDNA breaks induce epigenomic changes that accelerate the aging clock in mammals

molecular biology↗

Phenylpropionc acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity

ABSTRACTAcetaminophen (APAP) overdose causes hepatic injury and is major contributor to acute liver injury cases. To investigate potential roles of gut microbiota in APAP-induced liver injury, C57BL/6 mice from Jackson (JAX) or Taconic (TAC) were challenged with APAP. TAC mice were more susceptible to APAP toxicity, and this disappeared upon co-housing of JAX and TAC mice. When the cecum contents from JAX and TAC mice were transplanted to germ-free mice, the mice that received TAC gut microbiota exhibited more significant hepatotoxicity after APAP administration. Non-targeted metabolomic analysis using portal vein serum and liver tissue of the mice led to identification of 19 metabolites the levels of which are associated with JAX or TAC gut microbiota. A gut bacteria-derived metabolite phenylpropionic acid (PPA) levels in cecum contents and blood were higher in mice harboring JAX gut microbiota. PPA supplementation in drinking water alleviated APAP-induced hepatotoxicity in TAC mice. This was accompanied by reduced hepatic protein levels of cytochrome P450 (CYP) 2E1, the enzyme responsible for APAP bioactivation to a toxic metabolite. This illustrates a gut microbe-liver interaction mediated by a gut bacteria-derived metabolite in modulating drug-induced liver injury.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology↗

High-depth resequencing reveals hybrid population and insecticide resistance characteristics of fall armyworm (Spodoptera frugiperda) invading China

The rapid wide-scale spread of fall armyworm (Spodoptera frugiperda) has caused serious crop losses globally. However, differences in the genetic background of subpopulations and the mechanisms of rapid adaptation behind the invasion are still not well understood. Here we report a 393.25-M chromosome-level genome assembly of fall armyworm with scaffold N50 of 13.3 M consisting of 23281 annotated protein-coding genes. Genome-wide resequencing of 105 samples from 16 provinces in China revealed that the fall armyworm population comprises a complex inter-strain hybrid, mainly with the corn-strain genetic background and less of the rice-strain genetic background, which highlights the inaccuracy of strain identification using mitochondrial or Tpi genes. An analysis of genes related to pesticide- and Bt-resistance showed that the risk of fall armyworm developing resistance to conventional pesticides is very high, while remaining currently susceptible to Bt toxins. Laboratory bioassay results showed that insects invading China carry resistance to organophosphate and pyrethroid pesticides, but are sensitive to genetically modified maize expressing Cry1Ab in field experiments. Additionally, we found that two mitochondrial fragments are inserted into the nuclear genome, and the insertion event occurred after the differentiation of the two strains. This study represents a valuable advancement toward the analysis of genetic differences among subpopulations and improving management strategies for fall armyworm.

genomics↗

Placental Editome Profiling Reveals Widespread RNA-Editing Dysregulation in Preeclampsia

Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown, because RNA editing has rarely been studied in the placenta. Here, we have systematically profiled RNA editome on the placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The \"RNA editing events\" at two microRNA binding sites in 3-UTR of the LEP mRNA were generated, which could lead to increased expression level of LEP in trophoblast cells. Upregulation of LEP were also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia.

genomics↗

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Since the root cause of PE is thought to be located in the placentae, we carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for molecular features. We identified two functionally distinct sets of dysregulated genes in two major subtypes: metabolism-related genes, notably transporter genes, in early-onset severe preeclampsia and immune-related genes in late-onset severe preeclampsia, while the late-onset mild preeclampsia could not be distinguished from normal controls. A small number of dysregulated transcription factors may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors.

genomics↗

Isolation and Characterization of a Rhizobium Bacterium Associated with the Toxic Dinoflagellate Gambierdiscus balechii

Algae-bacteria associations are increasingly being recognized to be important in shaping the growth of both algae and bacteria. Bacteria belonging to order Rhizobiales are important symbionts of legumes often developing as nodules on plant roots, but have not been widely documented in association with algae. Here, we detected, isolated, and characterized a Rhizobium species from the toxic benthic dinoflagellate Gambierdiscus culture. The sequence of 16S rDNA showed 99% identity with that of Rhizobium rosettiformans. To further characterize the bacterium, we amplified and sequenced a cell wall hydrolase (CWH)-encoding gene; phylogenetic analysis indicated that this sequence was similar to the homologs of Martellela sp. and Hoeflea sp, of order Rhizobiales. We performed PCR using nifH primers to determine whether this bacterium can fix N2; however, the results of sequencing analysis showed that it was closer to chlorophyllide a reductase-encoding gene (bchX), which is similar to nifH. Results of 16S rDNA qPCR showed that compared to that in the early exponential phase, the abundance of this bacterium increased during the late exponential growth phase of Gambierdiscus. When the dinoflagellate culture was subjected to N limitation, the abundance of the bacterium represented by both 16S rDNA and CWH increased. Based on these results and published literature, it is apparent that this Rhizobium bacterium benefits from the association with Gambierdiscus by hydrolyzing and utilizing the extracellular organic matter exudates released by the dinoflagellate. This is the first report of Rhizobium species being associated with dinoflagellates, which will shed light on the algae-bacteria relationships.\n\nIMPORTANCEPhytoplankton are the undisputed primary producers in the aquatic ecosystems and contribute approximately half of the global net primary productivity.\n\nDinoflagellates are one of the most important phytoplankton in the marine ecosystems. Commonly, they do not exist autonomously in the marine environment but rather co-live with many bacteria that interact with dinoflagellates, producing a dynamic microbial ecosystem. Their interactions play a major role in important processes such as carbon fluxes and nutrient regeneration in the ocean, ultimately influencing the global carbon cycle and the climate. Hence, there is a need to understand the association and relationships between dinoflagellates and bacteria. Here, we tried to elucidate these interactions through isolating and characterizing a bacterium from a benthic toxic dinoflagellate culture. Our study is the first report of such bacterium being recorded to be associated with a dinoflagellate in this genus, providing new insights into the dinoflagellate-bacteria association for future research.

microbiology↗

A mathematical modeling approach to explore kinetics of Chimeric Antigen Receptor (CAR) T-cell Response in glioma: the CARRGO model

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of hematological cancers and is currently being investigated for solid tumors including high-grade glioma brain tumors. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumors. In this work we use a mathematical model of predator-prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor t-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, CAR T-cell proliferation and exhaustion, and CAR T-cell persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyzer to parameterize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted as compared to higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumor growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumor characteristics including tumor growth rate and antigen level to maximize therapeutic benefit. Statement of SignificanceWe utilize a mathematical model to deconvolute the nonlinear contributions of CAR T-cell proliferation and exhaustion to predict therapeutic efficacy and dependence on CAR T-cell dose and target antigen levels.

immunology↗

Initial data release and announcement of the Fish10K: Fish 10,000 Genomes Project

With more than 30,000 species, fish are the largest and most ancient vertebrate group. Despite their critical roles in many ecosystems and human society, fish genomics lags behind work on birds and mammals. This severely limits our understanding of evolution and hinders progress on the conservation and sustainable utilization of fish. Here, we announce the Fish10K project, an international collaborative project or initiative? aiming to sequence 10,000 representative fish genomes under a systematic context within ten years, and officially welcome collaborators to join this effort. As a step towards this goal, we herein describe a feasible workflow for the procurement and storage of biospecimens, and sequencing and assembly strategies. To illustrate, we present the genomes of ten fish species from a cohort of 93 species chosen for technology development.

genomics↗

Myt Transcription Factors prevent stress-response gene over-activation to enable postnatal pancreatic β cell proliferation and function

Although stress response maintains cell function and survival under adverse conditions, over-activation of late-stage stress-gene effectors causes dysfunction and death. Here we show that the Myelin Transcription Factors (Myt 1, 2, and 3 TFs) prevent this over-activation. Co-inactivating Myt TFs in mouse pancreatic progenitors compromised postnatal {beta}-cell function, proliferation, and survival, preceded by upregulation of late-stage stress-response genes Activating Transcription Factors (e.g., Atf4) and Heat Shock Proteins (Hsps). Myt1 binds the putative enhancers of Atf4 and Hsps, whose over-expression in mouse {beta} cells largely recapitulated the Myt mutant phenotypes. Moreover, Myt(MYT)-TF levels were upregulated in functional mouse and human {beta} cells by metabolic stress but downregulated in those of type 2 diabetic islets that display ATF4 and HSP over-activation. Lastly, human MYT knockdown caused stress-gene over-activation and death in Endo-{beta}H1 cells. These findings suggest that the Myt TFs restrict stress-response to physiologically tolerable levels in mice and human.

developmental biology↗

Hsa_circ_0001947 suppresses acute myeloid leukemia progression by sponging hsa-miR-329-5p and regulating CREBRF expression

Acute myeloid leukemia (AML) is a heterogeneous group of diseases resulting from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. Accumulating evidence has indicated that aberrantly expressed circular RNAs (circRNAs) are involved in cancer development and progression. However, their clinical values and biological roles in AML remain unclear. In this study, we identified the aberrantly down-regulated profile of hsa_circ_0001947 in AML through microarray analysis and validated it with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we explored the clinical significance, biological functions and regulatory mechanisms of hsa_circ_0001947 in AML patients. The results showed that lower hsa_circ_0001947 expression was positively correlated with higher leukemia cells in bone marrow or peripheral blood, indicating poor prognosis. Further, bioinformatics analysis demonstrated hsa_circ_0001947-hsa-miR-329-5p-CREBRF network. Down-regulation of hsa_circ_0001947 by siRNA promoted cell proliferation, inhibited apoptosis, reduced drug resistance of AML cells, and also decreased the expression of its targeted gene, CREBRF. The mimics of hsa-miR-329-5p reduced drug resistance and decreased the expression of CREBRF, while its inhibitor manifested anti-leukemia effects and increased CREBRF expression. In vivo studies revealed that silencing hsa_circ_0001947 promoted the tumor growth in BALB/c nude mice. Collectively, our findings suggest that hsa_circ_0001947 functions as a tumor inhibitor to suppress AML cell proliferation through hsa-miR-329-5p/CREBRF axis, which would be a novel target for AML therapy.

cancer biology↗

Multi-Region Brain Stimulation Optimization Using Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a type of noninvasive transcranial electrical brain stimulation. By optimizing the current distribution of each electrode on the scalp, the stimulation can be guided to a target brain region using a tDCS dense electrode array system. However, previous studies have yielded simple results using optimization schemes in single target stimulation cases. The detailed parameter settings for each optimization scheme and the associated simulation results have not been comprehensively assessed. In this study, we investigated parameter settings of optimization schemes in detail in both single target and multi-target cases. Two optimization schemes, minimum least squares (MLS) and maximum electrical field strength (ME), were examined in this study. MLS minimizes the squared errors between the expected electrical field and the estimated electrical field, whereas ME maximizes the electrical field strength in the target region. We constructed a five layer finite-element head model with 64 electrodes placed on the scalp according to the EEG 10/10 system for simulation. We evaluated the effects of stimulation using these two schemes under three conditions, 1) single target stimulation, 2) multi-target stimulation, and 3) multi-target stimulation under specific task activation, which shown that directly using MLS and ME scheme in multi-target stimulation case may lead to a wrong result. We also reported the improved results fixed by our proposed weighted MLS and weighted ME schemes which take detailed parameter settings into consideration. Our results indicate that the parameter settings in each optimization scheme greatly affected the final stimulation results, especially in the case of multi-target stimulation, and thus, indicate that the parameter settings of each optimization scheme should be carefully considered according to the expected stimulation mode. Our results also suggest that, by calculating the parameters through our proposed methods, the weighted ME and weighted MLS scheme can precisely distribute energy into each target brain region.

bioengineering↗

Lyb-2-4, a unique genomic region of hypervirulent carbapenem-resistant Acinetobacter baumannii

Acinetobacter baumannii is an important human pathogen due to its multi-drug resistance, but is usually with low-grade virulence. Although a mouse model revealed different virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen Peoples Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study should be very useful in advising the clinician to implement medical intervention earlier, and also making the worldwide surveillance of these hypervirulent CRAB strains easier.\n\nIMPORTANCEHypervirulent CRAB strains are expected to pose a threat to human health because infection of these strains is associated with high mortality and multidrug resistance. The rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other countries. Further research should focus on the mechanism of hypervirulence, the acquisition of this genomic region and the development of control measures to prevent further dissemination.

microbiology↗

A Pairwise Distance Distribution Correction (DDC) algorithm for blinking-free super-resolution microscopy

In single-molecule localization based super-resolution microscopy (SMLM), a fluorophore stochastically switches between fluorescent- and dark-states, leading to intermittent emission of fluorescence, a phenomenon known as blinking. Intermittent emissions create multiple localizations belonging to the same molecule, resulting in blinking-artifacts within SMLM images. These artifacts are often interpreted as true biological assemblies, confounding quantitative analyses and interpretations. Multiple methods have been developed to eliminate these artifacts, but they either require additional experiments, arbitrary thresholds, or specific photo-kinetic models. Here we present a method, termed Distance Distribution Correction (DDC), to eliminate blinking-caused repeat localizations without any additional calibrations. The approach relies on the finding that the true pairwise distance distribution of different fluorophores in an SMLM image can be naturally obtained from the imaging sequence by using distances between localizations separated by a time much longer than the average fluorescence survival time. We show that using the true pairwise distribution we can define and then maximize the likelihood of obtaining a particular set of localizations void of blinking-artifacts, generating an accurate reconstruction of the underlying cellular structure. Using both simulated and experimental data, we show that DDC surpasses all previous existing blinking-artifact correction methodologies, resulting in drastic improvements in obtaining the closest estimate of the true spatial organization and number of fluorescent emitters in a wide range of applications. The simplicity and robustness of DDC will allow it to become the field standard in SMLM imaging, enabling the most accurate reconstruction and quantification of SMLM images to date.

biophysics↗

Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

bioinformatics↗

Systematical analysis reveals the novel function of Cyp2c29 in liver injury

As a severe lethal cancer, hepatocellular carcinoma (HCC) usually originates from chronic liver injury and inflammation, in which the discovery of key genes is important for HCC prevention. Here, we analyzed the time serial (from 0 week to 30 weeks) transcriptome data of liver injury samples in diethylnitrosamine (DEN)-induced HCC mouse model. Through expression and function analyses, we identified that Cyp2c29 was a key gene continuously downregulated during liver injury. Overexpression of Cyp2c29 suppressed the NF-{kappa}B activation, proinflammatory cytokine production and hepatocyte proliferation by increasing its production 14,15-epoxyeicosatrienoic acid (14,15-EET). Furthermore, in vivo Cyp2c29 protected against liver inflammation in liver injury mice models by reversing the expression on functions of cell proliferation, metabolism and inflammation including suppressing NF-{kappa}B pathway and compensatory proliferation. CYP2C8 and CYP2C9, two human homologs of mouse Cyp2c29, were decreased in human HCC progression and positively correlated with HCC patient survival. Therefore, through systematical analysis and verification, we identified that Cyp2c29 is a novel gene in liver injury and inflammation, which may be a potential biomarker for HCC prevention and prognosis.

bioinformatics↗

Inference of Gene Regulatory Network Uncovers the Linkage Between Circadian Clock and Crassulacean Acid Metabolism in Kalanchoë fedtschenkoi

The circadian clock drives time-specific gene expression, allowing for associated biological processes to be active during certain times of the 24 h day. Crassulacean acid metabolism (CAM) photosynthetic plants represent an interesting case of circadian regulation of gene expression as CO2 fixation and stomatal movement in CAM plants display strong circadian dynamics. The molecular mechanisms behind how the circadian clock enabled these physiological differences is not well understood. Therefore, we set out to investigate whether core circadian elements in CAM plants were re-phased during evolution, or whether networks of phase-specific genes were simply connected to different core elements. We utilized a new metric for identifying candidate core genes of a periodic gene network and then applied the Local Edge Machine (LEM) algorithm to infer regulatory relationships between the candidate core clock genes and orthologs of known core clock genes in K. fedtschenkoi. We also used LEM to identify stomata-related gene targets for K. fedtschenkoi core clock genes and constructed a subsequent gene regulatory network. Our results provide new insights into the mechanism of circadian control of CAM-related genes in K. fedtschenkoi, facilitating the engineering of CAM machinery into non-CAM plants for sustainable crop production in water-limited environments.

plant biology↗

Low rate of follow-up colonoscopy after positive results of colorectal cancer screening in a Chinese urban core district

Colorectal cancer (CRC) is one of the most common cancers in China. In 2003, a systematic CRC registry that enables the determination of CRC incidence and mortality and a CRC screening project were introduced in the Jingan district of Shanghai by the municipal government. This study assessed the registry data to determine the status of CRC and CRC screening rates in the core district of an urban area of China. Data were retrieved from the Official registry information systems of Jingan district Shanghai Cance. The incidence and mortality of CRC, as well as population-based CRC screening rates, were analysed. Individuals who screened positive for CRC based upon results of a high-risk factor questionnaire (HRFQ) and a faecal immunochemical test (FIT) were selected for follow-up colonoscopy (CSPY). From the registry data collected between 2003 and 2013, the standardized incidence rate was 26.44/105, with a significant gender difference. The CRC standardized mortality rate was 10.08/105. In 2013, 17,866 individuals (21.6%) enrolled for CRC screening among the 82,602 candidate residents. The positive screening rate was 16.28% (2909/17866). Among the 2909 positives, 508 (17.5%) underwent follow-up CSPY. In 41.3% of these individuals (210/508), abnormal lesions were detected. Of these, 8 (1.57%) lesions were diagnosed as CRC, and 142 (28.0%) were identified as precancerous lesions. During the assessment period, both the incidence and mortality of CRC in the Jingan district were determined in the area of high CRC prevalence in Chin. Nevertheless, the rate of participation in CRC screening was low (21.6%), and the rate of participation in follow-up CSPY for individuals who screened positive was only 17.5%. Improved participation in CRC screening and follow-up CSPY is expected to lower the incidence and mortality of CRC significantly in the rural areas of China. (288)

cancer biology↗