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BACKGROUND:Transcranial magneto-acoustical electrical stimulation(TMAES)is a non-invasive,high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect,which can regulate the rhythmic oscillation of nerve activity,thereby affecting the brain's movement,cognition and other functions. OBJECTIVE:To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson's rats. METHODS:(1)Animal experiments:Twenty-four Wistar rats were randomly divided into four groups(n=6 per group).The rats in the normal control group received no intervention,while those in the normal stimulation group received TMAES(the average spatial peak pulse intensity:13.33 W/cm2,fundamental frequency:0.4 MHz,the number of fundamental wave cycles:1000,and pulse frequency:200 Hz).The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.After successful modeling,the rats in the model control group received sham TMAES stimulation in the prefrontal cortex,and those in the model stimulation group received TMAES in the prefrontal cortex,and the duration of stimulation was 2.0 minutes per day.After an interval of 8-10 minutes,the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups.The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80%for 3 consecutive days.(2)Modeling and simulation experiments:The cortical-basal ganglion circuit model under TMAES was established,and the ultrasonic emission period(5,10,20 ms),ultrasonic emission duty cycle(30%,50%,90%)and induced current density(20,50,100 μA/cm2)were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson's rats under different stimulation parameters. RESULTS AND CONCLUSION:(1)Animal experiments:The spatial learning ability of the rats in the normal control group was stronger than that of the model control group(P<0.001),the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group(P<0.05),and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group(P<0.01).The distribution of beta oscillation energy in the normal control group was more concentrated,and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group.The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups.Moreover,the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group.(2)Modeling and simulation experiments:the peak power spectral density of the beta band of healthy rats without stimulation(30 dB)was significantly lower than that of Parkinson's rats(55 dB).The power spectral density value generally decreased after stimulation.The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density.In addition,the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%.These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats,thereby improving motor function and decision-making cognitive function in rats.
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Objective @#To investigate whether fenoldopam (FNDP) ( an agonist of type 1 dopamine receptor) has a protective effect on thoracic aortic aneurysm ( TAA) in mice .@*Methods @#Three-week-old male C57BL/6J mice were treated with β-aminopropionitrile (BAPN) to induce TAA . The mice were divided into three groups : the con- trol group , the BAPN group , and the BAPN + FNDP group (FNDP inj ected intraperitoneally) . The incidence and survival rate of TAA were recorded . Gross anatomy of the whole aortae was ob served . Elastin staining was per- formed to assess morphological change , while immunohistochemistry was employed to evaluate the expressions of matrix metalloproteinase 2(MMP2) , matrix metalloproteinase 9( MMP9) and cluster of differentiation 68( CD68) respectively. Gelatin zymography was conducted to assess MMP2 and MMP9 activity. Reverse transcription-poly- merase chain reaction (RT-PCR) was performed to measure the mRNA expression levels of dopamine receptor D1(D1DR) , dopamine receptor d2 (D2DR) , dopamine receptor d3 (D3DR) , dopamine receptor d5 (D5DR) , in- terleukin-1β(IL-1β) , interleukin-6 (IL-6) , tumour necrosis factor-α (TNF-α) , monocyte chemoattractant pro- tein-1 (MCP-1) , alpha-smooth muscle actin ( α-SMA) and smooth muscle protein 22 -alpha (SM22α) .@*Results@#Compared to the control group , the BAPN group exhibited significant formation of TAA . Elastic fiber disruption was also ob served in the thoracic aortic wall , along with a significant decrease in the mRNA levels of D1DR and D5DR. The BAPN + FNDP group showed a significant reduction in the incidence of TAA formation and the rate of aneu- rysm rupture compared to the BAPN group . The disruption and rupture of elastic fibers in the thoracic aortic wall were significantly improved in the BAPN + FNDP group . The levels of MMP2 and MMP9 in the thoracic aortic wall significantly decreased , and the enzymatic activity of MMP2 in the serum was significantly reduced . Moreover , macrophage infiltration in the thoracic aortic wall was significantly reduced and the mRNA levels of IL-1β, IL-6 , TNF-αand MCP-1 also significantly decreased after FNDP treatment. There was no statistically significant differ- ence in the mRNA levels of α-SMA and SM22α.@*Conclusion @#FNDP shows an inhibitory effect on TAA progres- sion in mice , suggesting a potential of FNDP as a therapeutic agent for TAA .
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Noise pollution has become a common public health problem. The harm of noise exposure to human health cannot be ignored. Exposure to noise not only damages the auditory system but also affects the non-auditory system. At present, accumulating domestic and international epidemiological studies have suggested that noise exposure may be related to glycolipid metabolism disturbance. This article summarized recent epidemiological evidence of the association between noise exposure and glucose and lipid metabolism disorders, such as type 2 diabetes, obesity, metabolic syndrome, and hyperlipidaemia. The potential biological mechanisms connecting noise exposure to glucolipid metabolism were also introduced, e.g. noise as a stressor, sleep disorders, and intestinal flora regulation. This study discussed the impacts of noise exposure on glycolipid metabolism related diseases, providing a basis for further identifying noise related risk factors, conducting future related research, and formulating scientific and effective prevention and control measures.
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Transcranial magneto-acoustic-electrical stimulation is a new non-invasive neuromodulation technology, in which the induced electric field generated by the coupling effect of ultrasound and static magnetic field are used to regulate the neural rhythm oscillation activity in the corresponding brain region. The purpose of this paper is to investigate the effects of transcranial magneto-acoustic-electrical stimulation on the information transfer and communication in neuronal clusters during memory. In the experiment, twenty healthy adult Wistar rats were randomly divided into a control group (five rats) and stimulation groups (fifteen rats). Transcranial magneto-acoustic-electrical stimulation of 0.05~0.15 T and 2.66~13.33 W/cm 2 was applied to the rats in stimulation groups, and no stimulation was applied to the rats in the control group. The local field potentials signals in the prefrontal cortex of rats during the T-maze working memory tasks were acquired. Then the coupling differences between delta rhythm phase, theta rhythm phase and gamma rhythm amplitude of rats in different parameter stimulation groups and control group were compared. The experimental results showed that the coupling intensity of delta and gamma rhythm in stimulation groups was significantly lower than that in the control group ( P<0.05), while the coupling intensity of theta and gamma rhythm was significantly higher than that in the control group ( P<0.05). With the increase of stimulation parameters, the degree of coupling between delta and gamma rhythm showed a decreasing trend, while the degree of coupling between theta and gamma rhythm tended to increase. The preliminary results of this paper indicated that transcranial magneto-acoustic-electrical stimulation inhibited delta rhythmic neuronal activity and enhanced the oscillation of theta and gamma rhythm in the prefrontal cortex, thus promoted the exchange and transmission of information between neuronal clusters in different spatial scales. This lays the foundation for further exploring the mechanism of transcranial magneto-acoustic-electrical stimulation in regulating brain memory function.
الموضوعات
Animals , Rats , Acoustics , Electric Stimulation , Memory, Short-Term/physiology , Rats, Wistar , Theta Rhythm/physiology , Transcranial Direct Current Stimulationالملخص
Objective:Using bioinformatics analysis methods, the differential genes in situ hepatocellular carcinoma and metastatic foci and their involved metabolic pathways were screened to find new metabolic targets for liver cancer metastasis treatment. Methods:The data numbered GSE40367 of primary and metastasis liver cancer were downloaded from the gene expression omnibus (GEO) database. After the differential expressed genes were screened out, the differential expressed genes were enriched with gene ontology (GO) functions and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The STRING database and cytoscape software were used to analyze protein interactions. The changed metabolites in liver cancer metastasis were obtained from the research. Then the differential genes and metabolites were analyzed by MetaboAnalyst 4.0. Kaplan-Meier survival curve was used for survival analysis of the key genes on line.Results:A total of 564 differential expressed genes were selected from GSE40367, compared with tumors in situ, there were 287 up-regulated and 277 down-regulated in metastasis tumors. GO functions were enriched in processes such as monocarboxylic acid metabolism, fatty acid metabolism, and lipid transport. KEGG enrichment analysis showed that these differential genes were mainly concentrated in bile secretion, ABC transporters, cysteine and methionine metabolism, and gluconeogenesis. The combined analysis showed that the mainly relevant metabolic pathways were nicotinate and nicotinamide metabolism, phenylalanine metabolism, arginine biosynthesis and glycolysis and gluconeogenesis. Survival analysis of key genes found that CTH downregulation may be associated with a poor prognosis of liver cancer, while the high expression of PCK1 and AOX1 may be associated with a poor prognosis of liver cancer. Conclusion:The bioinformatics analysis reveals metabolic pathways related to liver cancer metastasis and the changed genes and metabolites in the pathway, which helps to understand the molecular mechanism of metastasis, and provides new targets for the treatment of metastasis liver cancer.
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Objective To analyze the therapeutic effect and prognostic factors of induction chemotherapy plus intensity-modulated radiotherapy (IMRT) with or without consolidation chemotherapy for esophageal squamous cell carcinoma (ESCC).Methods One hundred and eight patients with ESCC treated between January 2010 to August 2014 were analyzed retrospectively.All patients received IMRT and platinum-based chemotherapy.The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method and the univariate prognostic analyses were tested by the Log-rank test.The Cox proportional hazard model was used for multivariate prognostic analysis.Results The follow-up rate was 97.2%.The 1-,3-and 5-year survival rates were 76.9%,50.9% and 32.3% respectively,and the LC rates were 73.6%,58.5% and 54.9% respectively.The median OS with and without consolidation chemotherapy were 51 and 15 months (x2 =5.076,P=0.024),respectively.Multivariate analysis showed that clinical N staging,recent curative effect and consolidation chemotherapy were important prognostic factors for OS,and recent curative effect was associated with LC.The rates of acute grade 3 radiation-induced esophagitis,gastrointestinal side effects,myelosuppression and radiation-induced pulmonary injury were 7.4%,6.5%,12% and 0.9%,respectively,and no grade 4 occurred.The late toxicity was mainly radiation-induced pulmonary fibrosis.Conclusions Induction chemotherapy plus IMRT with or without consolidation chemotherapy is safe and effective in the treatment of ESCC.The addition of consolidation chemotherapy may help prolong the survival of some patients and further research is necessary.Individualized treatment should be selected for patients who cannot tolerate or refuse concurrent chemoradiotherapy.
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Objective@#To analyze the therapeutic effect and prognostic factors of induction chemotherapy plus intensity-modulated radiotherapy (IMRT) with or without consolidation chemotherapy for esophageal squamous cell carcinoma (ESCC).@*Methods@#One hundred and eight patients with ESCC treated between January 2010 to August 2014 were analyzed retrospectively. All patients received IMRT and platinum-based chemotherapy. The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method and the univariate prognostic analyses were tested by the Log-rank test. The Cox proportional hazard model was used for multivariate prognostic analysis.@*Results@#The follow-up rate was 97.2%. The 1-, 3- and 5-year survival rates were 76.9%, 50.9% and 32.3% respectively, and the LC rates were 73.6%, 58.5% and 54.9% respectively. The median OS with and without consolidation chemotherapy were 51 and 15 months (χ2=5.076, P=0.024), respectively. Multivariate analysis showed that clinical N staging, recent curative effect and consolidation chemotherapy were important prognostic factors for OS, and recent curative effect was associated with LC. The rates of acute grade 3 radiation-induced esophagitis, gastrointestinal side effects, myelosuppression and radiation-induced pulmonary injury were 7.4%, 6.5%, 12% and 0.9%, respectively, and no grade 4 occurred. The late toxicity was mainly radiation-induced pulmonary fibrosis.@*Conclusions@#Induction chemotherapy plus IMRT with or without consolidation chemotherapy is safe and effective in the treatment of ESCC. The addition of consolidation chemotherapy may help prolong the survival of some patients and further research is necessary. Individualized treatment should be selected for patients who cannot tolerate or refuse concurrent chemoradiotherapy.
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BACKGROUND:Recently, the effects of human umbilical cord mesenchymal stem cel s (hUCMSCs) and placenta-derived mesenchymal stem cel s (PDMSCs) on treatment of acute graft versus host disease (aGVHD) have been confirmed in some in vitro studies or animal models. But there are stil no reports comparing the therapeutic effects of these two cel types. OBJECTIVE:To compare the immunosuppressive function of hUCMSCs and PDMSCs in vitro or in a mouse aGVHD model. METHODS:(1) In vitro experiment. Human peripheral blood mononuclear cel s (PBMCs) were isolated and divided into four groups:PBMCs cultured alone, PBMCs stimulated with phytohaemagglutinin (PHA), PHA stimulated-PBMCs cocultured with hUCMSCs, PHA stimulated-PBMCs cocultured with PDMSCs. After 5 days, PBMCs proliferation and interferon-γlevel in cel supernatant were measured. (2) In vivo experiment. Fifty-seven BABL/C(H-2d) mice exposed to 8.5 Gy irradiation were randomly divided into five groups:only saline injection group, syngeneic bone marrow transplantation group, al ogeneic bone marrow transplantation group, aGVHD group, hUCMSCs treatment group, PDMSCs treatment group. The clinical aGVHD score, histopathology of skin, liver, and smal intestine, and survival time were analyzed at days 11, 14, 21 after transplantation. RESULTS AND CONCLUSION:(1) In vitro test:compared with the hUCMSCs, PDMSCs had stronger anti-inflammatory function. (2) In vivo test:The clinical scores on acute graft versus host disease were significantly lower in the hUCMSCs and PDMSCs treatment groups than that in the aGVHD group (P<0.05). The survival rates of mice were significantly increased in the hUCMSCs and PDMSCs treatment groups compared to the aGVHD group (P<0.05). Evident skin lesions were not found in al groups. Although smal intestine mucosal lesions were found in al groups, the damage level seemed similar. Notably, significant difference was found in the liver that multifocal necrosis and a large number of inflammatory cel s were seen in the aGVHD group, but less necrosis and inflammatory cel s in the hUCMSC and PDMSC treatment groups. In conclusion, hUCMSC and PDMSC are comparably effective in the treatment of aGVHD in mice.
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BACKGROUND:There are various methodstoinduceadipogenic differentiation ofbone marrow mesenchymal stem cels, and the main componentfor adipogenic induction isindomethacin or rosiglitazone. However, there is a lack of comparative studyonthe induction efficiency and mechanism among these methods. OBJECTIVE:Tocompare the adipogenic responses ofhuman bone marrow mesenchymal stem celsto different induction methods, and to analyze the mechanismunderlyingdifferent induction efficiency. METHODS:After isolation and purification,the adipogenic abilitiesof human bone marrow mesenchymal stem cels in threedifferentculture systemswere comparedby oil red O staining and lipogenic geneassay. At 0, 1, 3 and 7 days of adipogenensis, mRNA expressionsof PPARγ, C/EBPα, Adiponectin and Leptin were detected.At7 daysofadipogenensis, protein expressionsof PPARγ and C/EBPβ were detectedby western blot assay,andeffects ofDIMIversusDIMRonphosphorylationofPPARγatSer273were compared. RESULTS AND CONCLUSION:Findings from oil red O staining andreal-time PCRshowedthat DIMR significantlyinducedadipogenicdifferentiation of bonemarrow mesenchymal stem cels compared with DIM and DIMI at 7 daysofinduction. Western blot showed thattheprotein expressionsof PPARγ and C/EBPβ in the DIMIgroupwere significantly higher than those in the DIMRand DIM at 7days ofinduction. In addition, the ratio ofPPARγphosphorylation atSer273was lowerin the DIMR group thantheDIMI group.To conclude,DIMR has the most potential to induce early adipogenesis ofhumanbone marrow mesenchymal stem cels by weakening the phosphorylationof PPARγ-Ser273.
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BACKGROUND:The majority of rheumatoid arthritis treatment is chronic anti-arthritis drugs, biological agents and plant drugs. Among them, plant drugs have been widely concerned due to low cost and few adverse effects. OBJECTIVE:To observe the expression of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the synovium of col agen-induced arthritis rats, and explore the effect of Aconitum leucostomum Worosch. on the expression. METHODS:Forty-five rats were randomly divided into normal control group (8 rats) and model group (37 rats). The col agen-induced arthritis model was established with the injection of type II bovine col agen into the end of the tail and paws. After the success of modeling, the 24 successful model rats were randomly selected and divided into model group (8 rats), Tripterygium wolfprdi polyglycoside group (8 rats) and Aconitum leucostomum Worosch. group (8 rats). The arthritis index of the rats in the three intervention groups and one control group were evaluated weekly. After treated by intragastric administration for 4 weeks (Tripterygium wolfprdi polyglycoside group and Aconitum leucostomum Worosch. group were taken by the corresponding drug solution, model group and normal control group were taken by the same volume of physiological saline), the expressions of TNF-αand IL-1βin the synovium were tested by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group, the arthritis index of mice in Tripterygium wolfprdi polyglycoside group and Aconitum leucostomum Worosch. group was decreased significantly after treatment (P<0.05). The expression levels of TNF-αand IL-1βin the synovium of model group were significantly higher than those of the normal control group (P<0.05). After treatment with Aconitum leucostomum Worosch. and Tripterygium wolfprdi polyglycoside, the expression levels of TNF-αand IL-1βin the synovium was decreased compared with the model group (P<0.05). Experimental findings indicated that, the mechanism that Aconitum leucostomum Worosch. treats rheumatoid arthritis is related to the inhibition of TNF-αand IL-1β.
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Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
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Animals , Humans , Energy Metabolism , Glucose , Metabolism , Glycolysis , Neoplasms , Metabolism , Pathology , Pentose Phosphate Pathway , Physiologyالملخص
Objective To analyse serum proteomic patterns'differences in esophageal carcinoma patients by proteinchip technology and study its clinical value.Methods Surface-enhanced laser desorption /ionization proteomic patterns and WCX-2 protein chip were respectively used to detect the serum proteomic patterns in esophageal carcinoma patients according to before and after radiation,IMRT or 2-dimensional radiotherapy and metastasis or not.The data were analyzed by using Biomarker Wizard software.Results 8 differential protein peaks whose M/Z were 2863,3884.213,1699.600,1371.126,8454.341,1141.881,1473.377,2086.908 and 2785.016 were significant before and after radiotherapy.8 protein peaks whose M/Z were 3470.098,2011.529,3395.789,2639.055,1511.632,11488.520,9546.555 and 4783.831 were significant between IMRT and 2-dimensional radiotherapy.2 protein peaks whose M/Z were 3470.098,3395.789 were significant between metastasis and not metastasis.Conclusion Serum surface-enhanced laser desorption / ionization proteomic patterns analysis has good prospects in evaluating therapeutic effect and prognosis of esophageal carcinoma patients.
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ObjectiveTo observe the effect of indomethacin on the migration of breast cancer cell line MCF-7 in vitro and investigate the mechanism involved.MethodsThe migration of MCF-7 cell line stimulated with or without indomethacin were tested using transwell plates consisting upper and lower chambers separated by Millipore polycarbonate membrance filters with 8 μm pore sizes; the levels of chemokine receptor 4(CXCR4),cyclooxygenase(COX-2),epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF)expression in MCF-7 cell line were detected by flow cytometry,Real-time PCR and ELISA,respectively.Results Indomethacin decreased the migration ability of MCF-7 cell line significandy.CXCR4 membrane expression was significantly reduced in a time-dose dependent manner,and CXCR4,COX-2 and EGFR mRNA levels were significantly downregulated after indomethacin stimulation.However,exposure to indometahcin had no major effect on VEGF production of cells.ConclusionThe downregulation of CXCR4,COX-2 and EGFR expression might be the primary mechanism involved in the inhibitory effect of indomethacin on the migration of MCF-7 cell line.
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This research analyzed the current situation of English learning anxiety of TCM majors by means of conducting a questionnaire based on the English learning anxiety scale (ELAS).The questionnaire results showed that communication apprehension was most prominent in terms of extent and amount while test anxiety also accounted for an important part of anxiety.The research further analyzed the influences of English learning anxiety and proposed some measures to ease students' anxiety and to enhance learning efficiency from teachers' perspectives.
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Objective To investigate the clinical significance of combined detection of serum CEA, SCC, CYFRA21-1 before and after radiotherapy in esophagus carcinoma. Methods 226 cases of esophagus carcinoma patient were collected from November, 2006 to December, 2008. ELISA was used to detect the serum CEA, SCC and CYFRA21-1 of patients with esophagus cancer before and after radiotherapy. SPSS13.0 was used for the statistical analysis. Results The positive rate of CEA, SCC and CYFRA21-1 was 11.1 %, 16.8%, 27.4 %, respectively and the combined positive rate was 39.8 % from 226 patient serums before radiotherapy. The longer the lesion length, the later the clinical stage,the deeper the tumor invasion, the higher the mean value of serum CEA, SCC, CYFRA21-1 was. The mean value was lower in the early stage. The mean value of CEA, SCC and CYFRA21-1 was found to be well correlated with tumor size, TNM stage and depth of tumor invasion. Among three tumor biomarkers, the individual difference of CEA and CYFRA21-1 was bigger and the pathological stage and prognosis correlation with CYFRA21-1 was the best. The biomarker value dropped to the level below the normal in 76.7% patient out of 90 cases after radiotherapy. Conclusion The combined detection of serum CEA, SCC, CYFRA21-1 may be used as adjuvant diagnosis for esophagus cancer and has better clinical value for prediction to treatment and prognosis.