Deubiquitinating enzymes, reversing protein ubiquitination, most of the researches focused on the ifeld of molecular biology. However, it have not yet attracted enough attention in translational medicine research. In fact, target proteins of deubiquitinating enzymes affect the tumor progression through various ways, for example, cell apoptosis and autophagy, the link between inlfammation and cancer, tumor hypoxia, signal transduction, cell cycle regulation and DNA damage. This paper reviewed the research progress on the relations between deubiquitinating enzymes and the correlated factors of tumor.

Objective To study the expression of high molecular weight cytokeratin (CK34βE12) in breast carcinoma and the relationship between the high molecular weight cytokeratin expression and patient's prognosis. Methods We detected the high molecular weight cytokeratin expression in 100 patient's of breast cancer tissues and paracancerous breast tissue in 30 cases immunohistochemically. The relationship between the expression of high molecular weight cytokeratin in breast cancer tissues and age, menstrual status, estrogen receptor expression, progesterone receptor expression, histology grading, TNM staging, pathology type, and patient survival was analyzed. Results (1) There was no significant correlation between high molecular weight cytokeratin expression of breast -cancer tissues and age, menstrual status, estrogen receptor expression, progesterone receptor expression (all P>0.05). But the correlation was statistically significant between that expression and histology grading, TNM staging, pathology category (all P<0.05). (2) By univariate analysis, the 5-year disease-free survival rate in patients with negative expression was lower than those with positive expression(P<0.05). By multivariate analysis, the expression of high molecular weight cytokeratin was unfavorably related with tumor free survival. Conclusion The expression of high molecular weight cytokeratin in breast carcinoma tissues was correlated with biologic malignancies of breast cancer, the negative high molecular weight cytokeratin expression of breast cancer tissues predicts poor prognosis.

ObjectiveTo evaluate the significance of CK19 mRNA monitoring in peripheral blood of breast cancer patients.MethodsPeripheral blood samples were collected from 137 breast cancer patients preoperatively,one day post-operation,7 days,1,3,6,12,18,and 24 months after operation.RTPCR was used to detect CK19 mRNA expression.The relationships were analyzed between CK19 mRNA expression and treatment result, between CK19 mRNA expression and clinicopathological parameters.ResultsThere was no significant difference between the level of CK19 mRNA as tested preoperatively,and 1,7 days postoperatively(P ＞ 0.05 ).From one month and thereafter,CK 19 mRNA decreased significantly when compared with that immediate perioperatives ( P ＜ 0.05 ). Postoperative peripheral CK19 mRNA expression increased in those found with recurrent or metastasized tumors ( P ＜ 0.01 ). CK19 mRNA expression does not correlate with patient's menstrual status,estrogen receptor expression,progesterone receptor expression,HER-2 expression and Ki67 proliferation expression (P ＞ 0.05 ). But there was statistically significant correlation between CK19 mRNA expression and tumour size,histology grading,pathological type,lymph node metastasis ( P ＜ 0.01 ).ConclusionsIn breast cancer patients peripheral blood CK19 mRNA expression is correlated with risk clinicopathological parameters, and increases in patients with postoperative recurrence and tumor metastasis.

An on-line solid phase extraction-high performance liquid chromatography ( SPE-HPLC ) system was applied in the plasma pharmacokinetic study of highly active anti-cancer compound tyrosine kinase inhibitors (TEB-415) in mouse. The on-line SPE-HPLC method associated with Ultimate3000 system which was applied to the determination of the blood drug level of TEB-415 in mouse plasma. C18 column ( Venusil MP, 150 mm × 4. 6 mm, 5μm) was used as analytical column and the mobile phase consisted of acetonitrile-5 mmol/L monopotassium phosphate buffer ( pH 3 . 5 ) at a flow rate of 1 . 0 mL/min was used as the isocratic elution. An MF Ph-1 column (10 mm×4 mm, 5 μm) was used as on-line SPE column, and water and water-acetonitrile were used as the washing solvent and elution solvent respectively. The detection wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5. 2 software. The linear range of the calibration curve was between 100 and 20000 μg/L, and the limit of qualification was 20 μg/L. The extraction recovery was between 90 . 5% and 94 . 6%. The RSD of intra-day and inter-day precision was less than 3. 5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were between 91. 49% and 101. 96%. After oral medication, the mean peak time (Tmax) of TEB-415 in mice was 5. 29 h, and the mean maximum concentration ( Cmax) was 3403μg/L. The area under the curve ( AUC) of TEB-415 was 24600 μg/L·h. This drug's mean half-life was 3. 84 h, and its mean retention time (MRT) was 6. 56 h. These parameters suggested that TEB-415 had appropriate rate of absorption and elimination with preferable bioavailability.

Objective To explore the expression of COX-2,PD-ECGF and VEGF in gastric carcinoma tissue,and analyze and identify the relationship between the expression and tumor angiogenesis together with biological behaviour in gastric carcinoma.Methods ElivisionTM immunohistochemical method was performed to detect the expression of COX-2,PD-ECGF,VEGF and CD34,and evaluate the value of MVD in surgically resected gastric carcinoma specimens and biopsy tissues under gastroscope,including normal gastric mucosa tissues, metaplasia tissues and gastric mucosal atypical hyperplasia tissues. Clinicopathologic data of patients were analyzed retrospectively. Results The positive expression of COX-2, PD-ECGF,VEGF and MVD in gastric carcinoma were significantly higher than those in normal gastric mucosa, metaplasia or gastric mucosal atypical hyperplasia,and also their expression and MVD were closely related to lymph node metastasis and depth of invasion. The MVD in the groups of COX-2,PD-ECGF,VEGF positive-expression were significantly higher than those in negative-expression groups respectively. There were positive correlations among the expression of COX-2,PD-ECGF and VEGF in gastric carcinoma. MVD increased significantly when COX-2, PD-ECGF and VEGF coexpressed. Conclusion The expression of COX-2,PD-ECGF,VEGF and tumor angiogenesis participated in the genesis,invasion and metastasis of human gastric carcinoma.COX-2,PD-ECGF and VEGF participated in the tumor angiogenesis of gastric carcinoma. In the process of tumor angiogenesis and expression in gastric carcinoma, COX-2, PD-ECGF and VEGF could strengthen the effectiveness each other.They could strengthen the effective ness of tumor angiogenesis when they coexpressed. They could be selected as targets for tumor anti-angiogenesis treatment.

AIM:To explore the effect of Xiangshahewei Pill(Radix Aucklandiae,Rhizoma Cyperi,Fructus Amomi,etc.)on secretion in anorectic rat model induced by Fenfluramine.METHODS:Anorectic rat model was induced by Fenfluramine in dose of 15 mg/kg for 8 days.Xiangshahewei Pill was administered orally to the rats also for 8 days.The volume of gastric juice,total gastric acid,mucus,acidity of gastric acid and activity of pepsin of rats were measured.RESULTS:Xiangshahewei Pill could improve the turbulence of gastric secretion in anorectic rat induced by Fenfluramine.Xiangshahewei Pill in dose of 0.75 g/kg(P

Objective To investigate whether conventional protein kinase C (cPKC ) βⅡ-interacting collapsin response mediator protein-2 (CRMP-2) provides neuroprotection against cerebral ischemic (I) injuries. Methods Male BALB/c mice were randomly divided into normoxic control (Nor) , HPC, Nor + Sham, HPC + Sham, Nor + I and HPC + I groups (n = 6 per group). Using our HPC and MCAO mouse models, we applied immunoprecipita-tion, two-dimensional electrophoresis and mass spectrometry to characterize cPKCβⅡ-interacting proteins and combined with SDS-PAGE and Western blot to quantitatively analyze CRMP-2 phosphorylation and degradation levels in the brain of mice after HPC and MCAO. Results The expression level of 10 cPKCβⅡ-interacting proteins changed obviously in cerebral cortex of HPC mice when compared with Nor group. One of these proteins, CRMP-2 protein level increased in particulate fraction and decreased in cytosolic fraction of cerebral cortex of HPC mice. CRMP-2 phosphorylation level in ischemic core (Ic) of cerebral cortex decreased significantly ( P < 0. 05 , n = 6) as compared with that of Nor + sham group, but CRMP-2 phosphorylation level in HPC +I group increased significantly as compared with that of Nor +I group ( P < 0. 05, n = 6). In ischemic cortex, CRMP-2 degradation (proteolysis) was observed as the appearance of 55 ku breakdown products (BDP). However, the CRMP-2 degradation level, BDPs products decreased significantly in penumbra ( P) of ischemic cortex from HPC +I group when we compared with that of Nor +I group (P < 0. 05, n = 6 ). Conclusion CRMP-2 is involved in attenuating the decrease of CRMP-2 phosphorylation in ischemic core and in inhibiting its degradation in penumbra of cerebral cortex of mice thereby to lessen the ischemic injuries.

Objective To explore the inhibitory effective and mechanism on the proliferation and apoptosis of sorafenib in vitro gastric cancer MGC80-3 cells. Methods The inhibitory effective of sorafenib at different concentrations for gastric cancer cell MGC80-3 were analyzed by MTT assay. Apoptosis rate was observed by AnnexinV/PI staining. Re-sults The proliferation inhibition of sorafenib on gastric cancer MGC80-3 cell was time-dose dependent manner, the difference was statistically significant (P<0.05). Conclusion The apoptosis of gastric cancer MGC80-3 cells is different and the apoptotic rate is increased with the increase of sorafenib concentration.

Objective:To study the regulatory effect of miR-9 on the proliferation of breast cancer cells by targeting hexokinase 2 (HK2) .Methods:Breast cancer tissues and paracancer tissues were collected and the expression levels of miR-9 and HK2 were detected. MCF-7 cells were cultured and divided into blank control group, NC group, miR-9 group, NC-siRNA group and HK2-siRNA group. The cell viability, expression levels of HK2 and cleaved caspase-3 were detected, the targeted binding of miR-9 to HK2 was verifed.Results:the expression level of miR-9 in breast cancer was lower than that in paracancer tissue (0.52±0.08 vs 1.05±0.25, t=16.685, P<0.000) , and the expression level of HK2 was higher than that in paracancer tissue (0.73±0.14 vs 0.34±0.08, t=17.587, P<0.000) , and the expression level of miR-9 was negatively correlated with HK2; the OD490 level, the expression level of HK2 and the fluorescence activity of double luciferase reporter gene containing HK2 mRNA 3 'UTR in miR-9 group were lower than those in NC group (0.58±0.09 vs 1.04±0.21, 0.51±0.08 vs 1.18±0.24, 41.11±9.28 vs 148.28±29.59, t/P=4.027/0.007, 5.297/0.002, 6.912/0.001) , and the expression level of cleaved caspase-3 was higher than that in NC group (1.08±0.26 vs 0.42±0.09, t/P=4.797/0.003) . The OD490 level and the expression level of HK in HK-siRNA group were higher than that in NC-siRNA group, and the expression level of cleaved caspase-3 was higher than that of NC-siRNA group. Conclusion:miR-9 can inhibit the proliferation of breast cancer cells, and its mechanism may be related to the targeted inhibition of HK2 expression and the increase of downstream cleaved caspase-3 expression.

Traditional Chinese medicine(TCM)plays a unique role in preventive treatment of disease,treatment of chronic disease and recovery.Integrating modern science and technology and methods to carry out integrated and innovative research will help to bring the value of traditional Chinese medicine into full play.In recent years,with the rapid development of digital therapeutics such as artificial intelligence and wearable devices,digital therapeutics have emerged.Under the guidance of TCM theory,TCM integrates digital therapeutics technology methods,personalized treatment of patients through advanced program-driven software or combined with hardware devices,and improves patient compliance,gives full play to the advantages of TCM.This paper uses CiteSpace to visualize the research hotspots of digital therapeutics,combined with the literature and the website data of the Food and Drug Administration and the National Medical Products Administration,to sort out the application of digital therapeutics in the prevention,treatment and recovery of diseases,analyze the key technologies and core theories in the current application of digital therapeutics.And taking TCM pentatotherapy,kinesiatrics and aromatherapy as examples,this paper discusses the application forms of digital therapeutics under the guidance of TCM theory,and provides a preliminary paradigm for TCM digital therapeutics.