Tryptophan 2,3-dioxygenase (TDO)is the rate-limiting enzyme in the catabolism of Trp along the kynurenine pathway.Trp is mainly catabilized by the TDO in the liver,which could not only regulate the concentration of the Trp and suppress the T cells proliferation,but also participate in antibacterial action and inflammatory response.The metabolin kynurenines as an endogenous ligand of the AhR receptor,the TDO enzymes,Kyn and AhR form the TDO-Kyn-AhR pathway have effects of regulatory the growth of tumor.With the research of the mechanism of immune regulation goes futher,it is expected to be a promising prospect in cancer therapy and the immune tolerance of transplantation.We reviewed in the article,which summarized the TDO mediated catabolism of Trp and immunomodulatory effect.

Objective: To investigate the value of routine indexes of blood, biochemistry and coagulation in assessing microcirculation in children with sepsis, and explore the related mechanism. Methods: The clinical data of 187 children with sepsis from July 2013 to July 2018 in Wuxi Children′s Hospital of Jiangsu Province were retrospectively analyzed. The lactic acid, D- dimmer (DD), platelet distribution width (PDW), red blood cell volume distribution width (RDW), albumin, capillary refill time (CRT), simplify pediatric clinical illness score (PCIS) and prognosis were observed. The children were divided into 3 groups according to the simplify PCIS: non-severe group (simplify PCIS>80 scores, 96 cases), severe group (simplify PCIS 71 to 80 scores, 64 cases), and extremely severe group (simplify PCIS ≤ 70 scores, 27 cases); the children were divided into 2 groups according to the prognosis: survival group (161 cases) and death group (26 cases); the children were divided into 3 groups according to the CRT: capillary refilling better group (CRT<1.0 s, 99 cases), capillary refilling infaust group (CRT 1.0 to 2.9 s, 60 cases), capillary refilling bad group (CRT ≥ 3.0 s, 28 cases). Results: The lactic acid, DD, PDW, RDW and fatality rate in non-severe group, severe group and extremely severe group were gradually increased: (2.281 ± 1.103), (4.839 ± 2.154), (7.019±3.014) mmol/L; (2.103 ± 0.133), (3.632 ± 0.218), (5.179 ± 0.113) mg/L; 0.122 ± 0.010, 0.149 ± 0.011, 0.177 ± 0.016; 0.137 ± 0.012, 0.151 ± 0.018, 0.169 ± 0.021; 2.08% (2/96), 14.06% (9/64), 55.56% (15/27), while the albumin was gradually decreased: (34.21 ± 13.72), (30.38 ± 18.63), (22.37 ± 16.31) g/L, and there were statistical differences (P<0.01). The lactic acid, DD, PDW and RDW in survival group were significantly lower than those in death group: (3.127 ± 1.312) mmol/L vs. (6.837 ± 2.174) mmol/L, (2.473 ± 1.713) mg/L vs. (4.213 ± 1.101) mg/L, 0.124 ± 0.012 vs. 0.170 ± 0.023 and 0.148 ± 0.022 vs. 0.171 ± 0.017, while the albumin was significantly higher than that in death group: (33.59 ± 16.90) g/L vs. (19.92 ± 18.70) g/L, and there were statistical differences (P<0.01 or <0.05). The lactic acid, DD, PDW and RDW in capillary refilling better group, capillary refilling infaust group and capillary refilling bad group were gradually increased: (2.362 ± 2.131), (5.312 ± 1.114), (8.121 ± 2.213) mmol/L; (2.072 ± 0.213), (3.923 ± 0.178), (5.317 ± 0.517) mg/L; 0.119 ± 0.021, 0.153 ± 0.012, 0.171 ± 0.011; 0.127 ± 0.021, 0.148 ± 0.015, 0.168 ± 0.027; while the albumin was gradually decreased: (35.37 ± 14.11), (31.21 ± 15.13), (22.87 ± 15.22) g/L, and there were statistical differences (P<0.01). Conclusions The lactic acid, DD, PDW, RDW, ALB and CRT have some value in assessing microcirculation in children with sepsis, and the change of component and construction in microcirculation is the cause of developing of these indexes.

The alpha rhythm in electroencephalograph has been associated with the mental state of the brain. The aim of the present study was to analyze the complexity of the alpha activity in depression patients by Renyi entropy (RE) under two conditions, i.e., resting with eyes closed followed by a simple mental arithmetic. The EEGs were recorded in 20 depression patients and 20 age-matched control subjects. Results showed that the alpha activity of depression patients is more complex during resting and is more regular during the mental arithmetic than that of the controls. RE analysis can well characterize the alpha activity in depression patients and could be a valuable tool to study cognitive process and also a potential effective approach for the diagnosis of depression.
Adult ; Alpha Rhythm ; Depression ; physiopathology ; Electroencephalography ; Entropy ; Female ; Humans ; Male ; Signal Processing, Computer-Assisted

Objective To investigate the correlations between P53 expression and clinicopathologic factors and prognosis of Luminal breast cancer.Methods From January 2009 to December 2012,a total of 283 patients with Luminal breast cancer in the Shanghai General Hospital Affiliated to Shanghai Jiaotong Univer-sity were included.P53 expressions of them were assayed by immunohistochemistry.Survival analysis was applied using Kaplan-Meier curve and Log-rank test.Single factor analysis and mutiple-factor analysis were applied using Cox proportional hazard regression model.Results The rate of P53 expression was associated with tumor size (χ2 =6.285,P =0.043),lymph node metastasis (χ2 =15.881,P =0.000),histological grade (χ2 =8.132,P =0.043)and Ki-67 (χ2 =6.476,P =0.039),but it was not associated with age (χ2 =0.955,P =0.328),menopausal status (χ2 =3.808,P =0.051),pathological pattern (χ2 =0.847,P =0.655),estrogen receptor (χ2 =1.867,P =0.172),progesterone receptor (χ2 =0.937,P =0.333)and human epidermal growth factor receptor-2 (χ2 =0.110,P =0.741 ).In all the 283 patients,the 5-year relapse-free survival rates for P53-positive group and P53-negative group were 66.7% and 90.7% respectively (χ2 =12.609,P =0.000),while the 5-year overall survival rates were 84.4% and 93.4% respectively (χ2 =4.153,P =0.042),with significant differences.In Cox mutiple-factor analysis,lymph node metastasis (HR =2.484,95%CI:1.393-4.431,χ2 =9.497,P =0.002)and P53 over-expression (HR =3.627,95%CI:1.061-12.401,χ2 =4.220,P =0.040)were independent prognostic factors for the relapse-free survival of patients with Luminal breast cancer,and lymph node metastasis (HR =3.451,95%CI:1.891-6.297,χ2 =16.290,P =0.000)and higher histological grade (HR =2.806,95%CI:1.091-7.219,χ2 =4.582,P =0.032)were independent prognostic factors for overall survival.Conclusion P53 over-expression of patients with Luminal breast cancer is associated with prognostic factors such as lymph node metastasis and histological grade,which indicates the worse prognosis.

Objective To investigate the inhibitory effect of cordycepin on immune function injury in lung cancer rats after radiation therapy through JAK2/STAT3 signaling pathway. Methods Fifty rats were used to establish tumor-bearing model and other 10 rats were taken as normal group. After successful modeling, the rats were randomly divided into model group, radiotherapy group, cordycepin group, agonist group and agonist+cordycepin group (10 rats in each group). We compared tumor weight, tumor volume, tumor inhibition rate, IL-6, TNF-α, spleen index and thymus index, the number of T lymphocyte subsets, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression levels among all groups. Results Compared with normal group, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 in model group were increased, while spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with model group, tumor weight, tumor volume, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased in radiotherapy group, while IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased (P < 0.05). Compared with radiotherapy group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 protein expression were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with agonist+cordycepin group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Conclusion Cordycepin can effectively inhibit the immune function injury in lung cancer rats after radiation therapy, and may play a regulatory role by inhibiting the JAK2/STAT3 signal pathway.

Objective To establish a rat liver transplantation model under direct vision of single operator and to explore the effect of different perfusion methods on the quality of the donor liver. Methods On the basis of the "two-cuff method" established by Kamada, the operation details were improved to established the rat liver transplantation model. The recipient rats were divided into two groups according to different perfusion methods, group A (perfusion via abdominal aorta) and group B (perfusion via portal vein). The perfusion effect, operation time, operation success rate, postoperative liver function, liver graft pathological manifestations and survival were compared between the two groups. Results There were more residual red blood cells in sinus hepaticus in group B than in group A after perfusion. Both the donor liver perfusion time and donor operation time were longer in group A than those in group B, and the differences were statistically significant (both P < 0.01). The success rate of operation in group A and group B was 77% and 71%, respectively. At 3 d after liver transplantation in rats, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) of the rats in the two groups were significantly higher than normal. At 7, 30 d after operation, compared with group A, the levels of ALT, AST and TB in group B were significantly increased, and the differences were statistically significant (all P < 0.01-0.05). The liver pathological examination showed that the degree of inflammatory reaction in the liver and degree of destruction of liver tissue in group B were more severe than those in group A, but there was no significant difference in long-term survival rate between the two groups. Conclusions Although the perfusion time and donor operation time of rat liver transplantation model were slightly prolonged by means of abdominal aorta perfusion, the perfusion effect was better, which can reduce liver tissue damage after operation and restore liver function to normal levels more quickly.

Objective To investigate the effect of CC chemokine receptor 4(CCR4) on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mouse models.Methods Western blot was used to detect the expression of CCR4 in hepatocellular carcinoma cell line.Lentivirus was utilized to construct PLC/PRF/5 and SMMC-7721 cell lines stably overexpressing and silencing CCR4,which were verified by Western blot.The influence of CCR4 on the radiosensitivity of hepatocellular carcinoma cells was assessed by plate clone formation assay.The effect of CCR4 on the tumorigenesis in hepatocellular carcinoma cells in vivo was evaluated by tumorigenesis assay in nude mice.Results CCR4 was highly expressed in highly-metastatic hepatocellular carcinoma cells and lowly expressed in hepatocellular carcinoma cells with low metastases.The PLC/PRF/5 and SMMC-7721 cells,which stably overexpressed and silenced CCR4,were successfully established.Overexpression of CCR4 reversed the inhibitory effect of sorafenib radiotherapy on PLC/PEF/5,whereas knockdown of CCR4 could increase the radiosensitivity of SMMC-7721 to sorafenib.Overexpressing CCR4 could promote the tumorigenicity of PLC/PEF/5,whereas knockdown of CCR4 could inhibit the tumorigenicity of SMMC-7721 in nude mice.Conclusion CCR4 overexpression significantly reduces the radiosensitivity of PLC/PRF/5 and increases the tumorigenicity in nude mice,whereas knockdown of CCR4 considerably increases the chemosensitivity and radiosensitivity of SMMC-7721 and suppresses the tumorigenicity in nude mice.

Objective: To investigate the effect of silencing GRAMD1A and inhibiting STAT5 signaling pathway on the radiosensitivity of Huh7 cells in order to provide new ideas for the clinical combined therapy of hepatocellular carcinoma. Methods: The Huh7 cells silencing GRAMD1A was constructed by infecting lentivirus and verified by qPCR and Western blot. QPCR and luciferase reporter assays were used to detect the effect of silencing GRAMD1A on the expression of STAT5 and its downstream genes. Colony formation and apoptosis were detected to evaluate the effects of silencing GRAMD1A and STAT5 inhibitor SH-4-54 on cell radiosensitivity. Results: After 2 Gy exposure of the constructed Huh7 cells, the colony formation ability of the silencing GRAMD1A combined irradiation group was significantly lower than that of the negative control combined irradiation group, and the difference was statistically significant (t=8. 494, P<0.05). Silence apoptosis in the GRAMD1A combined irradiation group was significantly increased compared with the negative control combined irradiation group (t=3.560, P<0.05). After silencing GRAMD1A, the radiosensitivity of Huh7 cells was significantly increased, and the expression of STAT5 and its downstream genes was significantly reduced in cells.The survival rate of the SH-4-54 inhibitor combined irradiation group was significantly lower than that of the dimethyl sulfoxide combined irradiation group, and the difference was statistically significant (t=8.660, P<0.05). SH-4-54 inhibited STAT5 after passage, the radiosensitivity of Huh7 cells was significantly increased. Conclusions Silencing GRAMD1A could significantly enhance the radiosensitivity of Huh7 cells via STAT5 signaling pathway, indicating that GRAMD1A plays an important role in the development and progression of HCC. This finding may provide a new target for HCC therapy.

Objective To evaluate recurrence risk factors in postoperative breast cancer patients after 5-year adjuvant endocrine therapy.Methods From Jan 2006 to Dec 2011,a total of 327 patients were enrolled for this study.Kaplan-Meier curves were applied to estimate survival rates and COX's proportional hazards model to identify prognostic variables.Results Among these 327 eligible patients,42 (12.8％) patients suffered from distant metastasis and 34 (10.4％) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy.Survival analysis showed that patients with histologic grade 3 disease,lymph node metastasis,Ki-67 high expression,high TNM stage and radiotherapy were statistically significant with poorer relapse-free survival (RFS,P =0.000,0.003,0.000,0.003,0.034)and poorer distant metastasis-free survival (DMFS,P =0.000,0.002,0.000,0.002,0.023),respectively.In multivariate analysis,patients with histological grade 3 disease (P =0.002) and more than 3 positive nodes (P =0.032) were risk factors for lower RFS.However,only histological grade 3 (P =0.015) was risk factor for DMFS.Conclusions Late relapse after completion of 5-year adjuvant endocrine therapy was still common,patients with grade 3 disease and more than 3 positive nodes may benefit from extended endocrine therapy.