Dihydrotriazine derivatives display high anticancer activity and inducing apoptosis, ROS, and autophagy.

A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC50 = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e-treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents.

New ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo.

In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound 11b exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after intraperitoneal administration, which was better than celecoxib as a positive control. Molecular docking results unclose the rationale for the interaction of the compound 11b with COX-2 enzyme. Further studies revealed that compound 11b exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC50) value of 1.16 µM and selectivity index (SI = 64.66) value close to that of celecoxib (IC50 = 0.93 µM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent.

Effects of in ovo Injection of Astragalus Polysaccharide on the Intestinal Development and Mucosal Immunity in Broiler Chickens.

The purpose of this study was to examine the effects of in ovo injection of Astragalus polysaccharide (APS) on hatchability, body weight (BW), intestinal histomorphology, the number of IgA+ cells and sIgA content in intestine, and the expression of intestinal immune-related genes in broiler chickens. On day 18 of the incubation, a total of 960 live embryo eggs were weighed and randomly divided into 4 treatment groups: a control group and three APS groups. The eggs in the control group were injected with 0.5 mL physiological saline. The eggs in the APS groups were injected with 3 different amounts of APS in 0.5 mL physiological saline: 1 mg (APSL), 2 mg (APSM) and 4 mg (APSH). The solution was injected into the amnion of each egg. The results showed that in ovo injection of APS did not affect the hatchability but increased the body weight of the 14 d and 21 d chickens, with a significant increase observed in the APSM group (P < 0.05). At most time points, the villus height (VH) was increased (P < 0.05) and the crypt depth (CD) was decreased (P < 0.05) in the small intestine of the broilers, with higher VH/CD ratios in the APSL and APSM groups compared with the control group. The number of IgA+ cells in the mucosa and the secretory immunoglobulin A (sIgA) levels in the intestinal washings were higher in the APSM and APSH groups than in the APSL and control groups. The gene expression levels of interleukin (IL)-2, interleukin (IL)-4, interferon gamma (IFN-γ), and Toll-like receptor (TLR)-4 were significantly enhanced by APS stimulation at most time points (P < 0.05). These results indicated that in ovo injection of APS has the potential of promoting intestinal development and enhancing intestinal mucosal immunity of broiler chickens in the early stage after hatching.

Antidepressant-like Effect of a Chalcone Compound, DHIPC and Its Possible Mechanism.

DHIPC (2,4-dichloro-2´-hydroxyl-4´,6´-diisoprenyloxychalcone) is a new chalcone compound. In this study, its antidepressant-like activity of compound DHIPC was evaluated by the forced swimming test and the tail suspension test in mice. The results showed that DHIPC significantly reduced the immobility time for 2 h after treatment through the oral administration at dose of 10, 20, and 30 mg/kg in the forced swimming test and the tail suspension test, indicating a significant antidepressant-like effect. The maximal effect was obtained at 30 mg/kg, which is similar to the positive control fluoxetine. The main monoamine neurotransmitters and their metabolites in rat brain were also simultaneously determined. It was found that DHIPC significantly increased the concentrations of the main neurotransmitters serotonin and noradrenalin, and also significantly increased 5-hydroxyindoleacetic acid contents in hippocampus, hypothalamus, and cortex in brain part. So, the probable mechanism of action of DHIPC is thought to be related to increase in serotonin and noradrenalin in the brain.

A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk.

Genetic variants found in DNA repair genes (ERCC1, rs3212986; ERCC2, rs13181; ERCC4, rs1800067; ERCC5, rs17655; XRCC1, rs1799782, rs25487, rs25489; XRCC3, rs861539) have been reported to have an ambivalent association with the development of glioma. In the present study, a meta-analysis was conducted to confirm the relationship, taking heterogeneity of population into consideration. We analyzed 21 articles of 6 genes along with 8 single nucleotide polymorphisms (SNPs) (24,078 cases and 30,926 healthy individuals), which assessed the relationship between nucleotide excision, base excision, double-strand break repair gene, and the development of glioma under five models. All statistical analysis was implemented by the software of R 3.2.1, and the relationships between key polymorphic loci in DNA repair genes and glioma were quantified by the pooled odds ratio (OR) and 95 % confidential intervals. Overall, the synthesized evidence demonstrated that the SNP of rs13181 and rs1799782 significantly increased the risk of glioma whereas SNP of rs1800067 were significantly associated with a decrease in the risk of glioma. Additionally, subgroup analyses of 8 SNPs by ethnicity indicated that the mutation of rs13181, rs1800067 were apparently protective factors of glioma among Asians, while the mutation of rs13181 was a risk factors of glioma in Caucasians. Furthermore, the mutation of rs1799782 significantly raises the risk of glioma for Asian. Our study suggested that rs13181*C and rs1799782*A are risk alleles for glioma; rs1800067*A are beneficial alleles for decreased susceptibility to glioma. Future studies with large sample size and other races are strongly recommended to confirm the results from this study.

Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1.

Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC)-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1) promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC.

Schidandrin B kills tumor cells by initiating apoptosis in glioma SHG-44 cells.

OBJECTIVE: To observe the proliferation inhibition, cell cycle, and apoptosis of human glioma cell line SHG-44 treated with different concentration of Schidandrin B and explore the effect of Schidandrin B on glioma SHG-44 cells. METHODS: Glioma SHG-44 cells were treated with Schidandrin B (0, 50, 100 or 200 µg/mL) for 24, 48, 72 and 96 h, and cells were treated with vehicle as control. Viability of cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis; cell cycle was examined with flow cytometry assay; apoptosis was detected with annexin V assay. Bax and caspase-3 proteins expression were checked by Western blot. RESULTS: MTT analysis showed that viability of glioma SHG-44 cells significantly decreased after exposure to Schidandrin B for the indicated time. Flow cytometry revealed that the number of cells in the sub G1 phase was increased, however, the number of cells in G0/G1, S and G2/M phases were decreased after treatment with 50, 100 or 200 µg/mL Schidandrin B, compared with the respective control group. Annexin V analysis confirmed that apoptosis rates of the control group, 50, 100, and 200 µg/mL Schidandrin B group were 1.76%±0.47%, 13.98%±5.05%, 19.64%±5.53% and 63.28%±6.88% respectively, apoptotic rate increased significantly with dose-dependent manner, and apoptosis of cells were observed under the inverted microscope after 100 µg/mL Schidandrin B treatment. Bax and caspase-3 protein were highly expressed in Schidandrin B group compared with the control group. CONCLUSION: The apoptosis could be induced by different concentration of Schidandrin B on glioma SHG-44 cells, and the mechanism may be directly excited by Schidandrin B in glioma SHG-44 cells through activating mitochondrial pathway.

Over Expression of BCL2 and Low Expression of Caspase 8 Related to TRAIL Resistance in Brain Cancer Stem Cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been investigated as an effective agent to treat various cancers. Cancer stem cells are resistant to TRAIL treatment, but the mechanism of TRAIL resistance remains unknown. In this study, brain cancer stem cells were isolated by CD133 magnetic sorting, and the number of CD133 positive cells detected by flow cytometry. The self-renewing capacity of brain cancer stem cells was examined by a neurosphere formation assay, and the percentage of cell death after TRAIL treatment was examined by an MTS assay. Expression of DR5, FADD, caspase 8 and BCL2 proteins was detected by western blot. The amount of CD133 positive cells was enriched to 71% after CD133 magnetic sorting. Brain cancer stem cell neurosphere formation was significantly increased after TRAIL treatment. TRAIL treatment also reduced the amount of viable cells and this decrease was inhibited by a caspase 8 inhibitor or by the pan-caspase inhibitor z-VAD (P<0.05). Brain cancer stem cells expressed lower levels caspase 8 protein and higher levels of BCL2 protein when compared with CD133 negative cells (P<0.05). Our data suggest that TRAIL resistance is related to overexpression of BCL2 and low expression of caspase 8 which limit activation of caspase 8 in brain cancer stem cells.

Life-threatening complications of ascariasis in trauma patients: a review of the literature.

BACKGROUND: Ascariasis is one of the most common human parasitic infections worldwide. In some rare cases, ascariasis may cause serious consequences even sudden death. This study was undertaken to review the life-threatening complications of ascariasis in trauma patients reported in the literature. DATA SOURCES: Relevant articles about ascariasis and trauma were searched from Pubmed, Google scholar, Scirus, and Wanfang databases. RESULTS: Twenty-four patients with ascariasis were collected from 21 articles searched. Most of these patients were from tropical and subtropical countries. Of the 24 patients, 12 were children. Their major complications occurred in the airway passage and digestive tract. There were 3 fatal cases in these patients. Twelve of the 24 patients described in 10 articles were reported in the last 10 years. CONCLUSIONS: Early diagnosis and prompt intervention are essential to minimize the high morbidity and mortality of these serious complications in trauma patients. Physicians should be aware of the possibility of Ascaris infection in a trauma patient from endemic area of ascariasis. History of Ascaris infection and routine examination of feces for Ascaris eggs may be helpful to make a correct diagnosis.

Pulmonary hypertension risk in patients with hemoglobin h disease: low incidence and absence of correlation with splenectomy.

Pulmonary hypertension (PHT) is a common complication for patients with ß thalassemia intermediate (TI), especially splenectomized patients. However, the frequency and risk factors of PHT in patients with hemoglobin H (HbH) disease is unknown. The purpose of this study was to identify the prevalence of PHT risk manifested as tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s in patients with HbH disease and its correlation with splenectomy. One hundred and ninety-eight patients with HbH disease who visited the 303rd Hospital of the People's Liberation Army (Nanning, China) were investigated. Thirteen subjects (6.5%) were diagnosed as having a risk of PHT. Regression analyses showed that the prevalence of PHT risk was correlated only with age (r = 0.195, p = 0.006) and not with splenectomy. The risk of PHT in patients older than 35 years was 5.7 times (range 1.8-18.6) greater than that for patients younger than 35 years. For splenectomized patients compared to those with HbH disease, patients with TI had a higher frequency of PHT risk, higher nucleated red blood cell counts (46.03 ± 41.11 × 10(9)/l vs. 0.18 ± 1.19 × 10(9)/l, p < 0.001) and a higher platelet counts (837.6 ± 178.9 × 10(9)/l vs. 506.7 ± 146.2 × 10(9)/l, p < 0.001). PHT risk is low in patients with HbH disease and does not correlate with splenectomy. Patients older than 35 years should be monitored regularly.

[Efficacy of Schizandra chinesis polysaccharide on cyclophosphamide induced dyszoospermia of rats and its effects on reproductive hormones].

OBJECTIVE: To explore the efficacy of Schizandra Chinensis polysaccharide (SCP) on cyclophosphamide (CTX) induced dyszoospermia of rats and its effects on reproductive hormones. METHODS: SCP was extracted by ethanol-alkali solution. Fifty male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the low dose SCP group (100 mg/kg), the middle dose SCP group (200 mg/kg), and the high dose SCP group (400 mg/kg). Except the normal control group, the dyezoospermia rat model was established by peritoneal injection of CTX at the daily dose of 80 mg/kg, once daily for 5 successive days. After modeling, SCP was intragastrically administered at corresponding dose to the three SCP groups. Equal volume of normal saline was given to rats in the normal control group and the model group by gastrogavage. All the medication was performed once daily for 60 successive days. The blood serum and testis were withdrawal 24 h after the last intragastric administration. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in the testis homogenate were determined by enzyme linked immunosorbent assay. The sperm count, the motility rate, and the teratospermia rate were compared. The morphology of the testis was observed using HE staining. RESULTS: Compared with the normal control group, the sperm count and the motility rate decreased, the teratospermia rate increased, the serum levels of FSH and LH increased, the T content in the testis homogenate decreased in the model group, showing statistical difference (P <0.01). Compared with the model group, the sperm count and the motility rate increased, the teratospermia rate decreased, the serum levels of FSH and LH decreased, the T content in the testis homogenate increased in the model group, showing statistical difference (P <0.01, P <0.05). All the indices showed dose-dependent manner in the SCP groups. The histological results showed the pathological injury in the testicular tissue was improved in all SCP groups. CONCLUSION: SCP showed obvious therapeutical effects on CTX induced dyszoospermia in rats, and its mechanisms might be correlate with recovering the regulation function of hypothalamus-hypophysis-gonad axis.

Evaluation of anticonvulsant activity of QUAN-0806 in various murine experimental seizure models.

A new quinoline derivative, QUAN-0806 (7-hexyloxy-5-phenyl-1,2,4-triazolo[4,3-alpha]quinoline) was tested for anticonvulsant activity using the maximal electroshock seizure (MES) and the rotarod neurotoxicity (Tox) tests in mice. The MES test showed that QUAN-0806 exhibited higher activity (ED50 = 6.5 mg/kg) and lower toxicity (TD50 = 228.2 mg/kg), resulting in a higher protective index (PI = 35.1) than the reference drugs phenytoin, carbamazepin, phenobarbital, and valproate. In addition, QUAN-0806 was found to exhibit significant oral activity against MES-induced seizures with low oral neurotoxicity in mice. QUAN-0806 was tested in chemically induced models (pentylenetetrazole, PTZ; isoniazid, ISO; 3-mercaptopropionic acid, 3-MPA; and strychnine, STRYC) to further investigate the anticonvulsant activity. QUAN-0806 produced significant antagonistic activity against seizures induced by PTZ, 3-MPA, and ISO, suggesting that QUAN-0806 influences GABAergic neurotransmission by activating glutamate decarboxylase (GAD) or inhibiting (GABA)-a-oxoglutarate aminotransferase (GABA-T) in the brain.

Synthesis and anticonvulsant activity of N-(2-hydroxy-ethyl)amide derivatives.

A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.

[The causes of death and risk factors in patients of war wound and trauma of extremities by logistic regression model].

OBJECTIVE: To explore the causes of death and risk factors in patients of war wound and trauma of extremities. METHODS: This retrospective study involved 352 patients of war wound and trauma of extremities admitted to 303rd Hospital of People's Liberation Army during the period between 1968 to 2002. All the data were reviewed and the causes of death of 15 patients were analyzed by autopsy, and a computer's logistic regression model analysis was performed to approach the risk factors of death. RESULTS: Fifteen of the three hundred and fifty-two patients were died (4.3 %). The causes of death included acute renal failure (ARF) (46.7%, 7/15), lung embolism (20.0%, 3/15), clostridial myonecrosis (20.0%, 3/15) and multiple organ system failure (MOSF) (13.3%, 2/15). In the univariate analysis, the risk of death increased by shock, time admitted to hospital, amputation, time of tourniquet, associated injury of head, thoracic region, abdomen or blood vessel (P < 0. 05). In the logistic regression model analysis, shock and amputation were the two factors most strongly associated with the death of patients of war wound and trauma. (P < 0. 05). CONCLUSION: Acute renal failure (ARF) was the main cause of death of patients of war wound and trauma of extremities. Its should be helpful for minimize the mortality of patients of war wound and trauma to manage the shock in time and have a correct choice of amputation promptly.

[Evaluation of the efficacy of phenobarbital in treatment of epilepsy in rural areas: study of 2455 patients in rural China].

OBJECTIVE: To evaluate the efficacy of phenobarbital in treatment of patients with convulsive forms of epilepsy in rural areas and to develop a suitable relevant model for rural China. METHODS: A demonstration protocol was conducted in the rural areas of 8 counties from 6 provinces and municipality in China, Heilongjiang, Ningxia, Henan, Jiangsu, Shanxi, and Shanghai from December 2001 to June 2004. Epidemiological investigation of the prevalence and treatment gap of epilepsy was carried out. Patients with convulsive forms of epilepsy thus screened underwent treatment of phenobarbital. Physicians of township hospitals received short-term training to be in charge of the treatment and regular follow-up of the patients. RESULTS: A total of 2455 patients with generalized tonic-clonic seizures in these 6 rural areas were screened and entered the treatment group. 347 patients (26.2%) had been seizure-free during the period of these 2 years, 415 patients (31.3%) had their seizure frequencies decreased by > 75% as compared with those during the period of 6 months before treatment, and the conditions of 26.1% of the patients did not change or even became worse. About 26.1% of the patients had mild side effects, 3.7% had moderate side effects, and only 0.3% had severe side effects when the dosage of phenobarbital in the first 3 months was increased. 597 patients (24.3%) withdrew from the treatment group because of various reasons. CONCLUSION: This protocol was suitable to the rural areas of China. The trained physicians are capable of fulfilling the task to treat the patients with epilepsy. Phenobarbital is an effective drug for most patients with convulsive seizures and has no severe side effect.

[Research on induced differentiation of human bone marrow mesenchymal stem cells into vascular endothelial cells].

AIM: To analyze gene expression difference between human mesenchymal stem cells and umbilical vein endothelial cells, to discuss the feasibility of inducing hMSCs to differentiate into endothelial cells through in vitro gene transfection as well as the use and prospective as a seeding cell source of vascular tissue engineering. METHODS: hMSCs and hUVECs were isolated, expanded in culture, and characterized by flow-cytometry, immunocytochemistry, immunofluorescence and transmission electron microscopy (TEM). Differential analysis of gene expression profiles between them was performed by Biostar H-40 cDNA microarrays. The properties of VEGF 165 transfected were also detected with RT-PCR, ELISA et al. RESULTS: Nearly 86% genes were coexpressed in both cells and hMSCs expressed typical endothelial antigen marker of EC. After VEGF165 transfection, hMSCs (or committed hMSCs) were positive for CD31. To different extent, the expression of CD44 was down regulated and CD34, FVIIIAg, Flt-1 up regulated. CONCLUSION: Generation of functional EC or tissue engineered blood vessels from human MSCs is feasible utilizing an in vitro environment gene transfection.

[Relationship between the expression of O6-methylguanine-DNA methyltransferase in glioma and the survival time of patients].

BACKGROUND & OBJECTIVE: Previous studies showed that the DNA-repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) is one of drug resistant factors that affect chemosensibility of glioma. This study was to analyze the relationship between the expression of MGMT in glioma and the survival time of patients,and supply references to make molecular classification for glioma based on drug resistant mechanism. METHODS: MGMT expression in 311 glioma specimens was examined by tissue array technology and immunohistochemistry method, all patients had been followed up for 5 years, and the materials were analyzed statistically. RESULTS: The positive expression of MGMT was 126 in 311 gliomas (40.51%), among them, 61 in 121 astrocytomas (50.41%), 18 in 70 oligodendrogliomas (25.71%), 18 in 64 oligoastrocytomas (28.13%), 29 in 56 glioblastomas (51.79%); 68 in 186 grade I-II gliomas (36.56%), and 58 in 125 grade III-IV gliomas (46.40%). The difference of MGMT expression between grade I-II and grade III-IV gliomas was significant (P< 0.001). According to Kaplan-Meier's survival curves and log-rank test, patients with MGMT expression showed a shorter survival time than those with no MGMT expression (P< 0.05). CONCLUSION: MGMT expression in glioma correlates with histopathological type and tumor grade. Patients with MGMT expression show a shorter survival time than those with no MGMT expression.

Colonoscopic screening and follow-up for colorectal cancer in the elderly.

AIM: To improve the prevention and treatment of senile patients with colorectal cancer by evaluating the importance of colonoscopy in clinical screening and follow-up. METHODS: Clinical screening of colonoscopy was performed for 2196 patients aged 60-90 years old according to the protocol,and 1740 of them (79.2%) were followed-up. RESULTS: Colorectal cancer was found in 52 patients, and the detectable rate was 2.4%. Among them, 19 were diagnosed as early colorectal cancer, accounting for 36.5% of the detected colorectal cancer. Among the followed-up patients, early colorectal cancer was found in 9, accounting for 45.0% of the detected colorectal cancer. The resectable rate and 5 years survival rate of colorectal cancer were 97.7% and 80.9% respectively. The incidence of complication was 0.05%, and the successful rate of cecum intubation was 98.9%. CONCLUSION: Colonoscopic screening and follow-up of the elderly for colorectal cancer and pre-cancerous lesion (adenomatoid polyp) can increase the detectable rate of early colorectal cancer and improve its prevention and treatment.