Objective To investigate the effect of a multi-target protein tyrosine kinase inhibitor,Ponatinib,on proliferation,homogeneity adhesion and migration ability of human liver cancer cell line SK-Hep-1.Methods SK-Hep-1 cells were cultured routinely and added with 24 tyrosine kinase inhibitors such as Ponatinib respectively,and the effect of Ponatinib on the survival and proliferation of SK-Hep-1 cells was detected by MTT assay.SK-Hep-1 cells were cultured routinely until the fusion degree reached 90%,then added with 0.1,0.5 and 1.0 μmol/L Ponatinib respectively,and the control group(without Ponatinib) was set up.The effect of Ponatinib on adhesion ability of SK-Hep-1 cells was detected by cell slow aggregation assay and dissociation assay,while the effect on migration ability by scratch test,and the effect on E-cadherin protein expression in SK-Hep-1 cells by Western blot.Results All 24 tyrosine kinase inhibitors inhibited SK-Hep-1 cells,among which Ponatinib showed the strongest inhibitory effect with a IC_(50) of(0.288±0.044) μmol/L.Compared with the control group,the number of cell mass(t=16.143,44.002 and 44.853 respectively,each P <0.001) and N_(TC)/N_(TE) [ratio of single cell number(N) after digestion by trypsin containing EDTA(TE) and CaCl_2(TC)](t=4.276,10.625 and 27.571 respectively,each P <0.05) decreased significantly and E-cadherin protein expression increased significantly(t=-3.757,-4.561and-6.922 respectively,each P <0.05) in 0.1,0.5 and 1.0 μmol/L Ponatinib groups;Scratch migration rate significantly decreased in 0.5 and 1.0 μmol/L Ponatinib groups(t=6.272～16.733 respectively,each P <0.01),while there was no significant difference in 0.1 μmol/L Ponatinib group(t=0.473 and 0.872 respectively,each P> 0.05) after 24 h and 48 h of scratch.Conclusion Ponatinib inhibited proliferation and migration of SK-Hep-1 cells and promoted cell adhesion.

Objective To evaluate the effect of tyrosine kinase inhibitor BGJ398 on the proliferation,apoptosis and migration of human hepatocellular cancer Huh-7 cells and explore the mechanism.Methods The effects of 10 tyrosine kinase inhibitors on the survival of Huh-7 cells were detected by MTT assay,and the sensitivity of Huh-7 cells to BGJ398 was analyzed by single-target kinetic equation and biphasic kinetic equation respectively.Huh-7 cells were added with 10,30 and 90 nmol/L BGJ398 respectively,and the control group(without drugs)was set.The effects of BGJ398 on the apoptosis and cell cycle of Huh-7 cells were detected by flow cytometry after culturing at 37℃for 24 h,the effect on the migration ability was detected by wound healing assay and the effect on the expression of multiple pathway-related proteins was detected by Western blot.Results All of 10 tyrosine kinase inhibitors inhibited the proliferation of Huh-7 cells,among which Huh-7 cells were most sensitive to BGJ398 and the IC_(50)was(0.020±0.013)μmol/L;The response of Huh-7 cells to BGJ398 was composed of two phases with F_1 accounted for 92.8%(K_(d1)was 36 nmol/L)and F_2 accounted for 7.2%(K_(d2)>1 000μmol/L).Compared with the control group,the apoptosis rate and the percentage of Huh-7 cells in G1 phase increased significantly in 30 and 90 nmol/L BGJ398 groups(t=-6.407～-4.459,each P<0.05),while the percentage of Huh-7 cells in S phase decreased significantly in 10,30 and 90 nmol/L BGJ398 groups(t=2.982,7.859 and 12.425,respectively,each P<0.05);After 24 and 48 h of scratching,the scratch area of 30 and 90 nmol/L BGJ398groups decreased significantly(t=5.376～18.197,each P<0.05);The expression levels of phosphorylated fibroblast growth factor receptor(FGFR)and phosphorylated extracellular signal-regulated kinase 1/2(Erk1/2)protein decreased significantly in 30 and 90 nmol/L BGJ398 groups(t=4.015～6.729,each P<0.01).Conclusion BGJ398 can inhibit the proliferation and migration of human hepatocellular cancer Huh-7 cells,induce apoptosis and cell cycle arrest,which might be achieved by inhibiting FGFR phosphorylation and MAPK signaling pathway.BGJ398 is expected to be a potential agent for the treatment of hepatocellular cancer.

Human cytomegalovirus(HCMV) is a ubiquitous herpesvirus.It is always a serious pathogen in immunosuppressed individuals,and also the most common and harmful agent causing congenital infection and birth defects.Biological functions of the encoded proteins in HCMV UL/b' region,which is deleted in the HCMV laboratory AD169 strain,have been explored in depth in recent years,and the results demonstrate that the proteins have important roles in HCMV virulence,transmission,tropisms and immune escape and so on.UL133-UL138 locus can promote to establish and maintain HCMV latent infections,and pUL1 38 is the first HCMV protein demonstrated to promote infection with the hallmarks of latency in CD34 + hematopoietic progenitor cells (HPC).Therefore,the products expressed by the gene of HCMV UL/b' region are crucial in the course of HCMV infection.This article reviews the genetic structure and biological functions of encoded proteins in HCMV UL/b' region,especially pULl38 which is related with HCMV latent infections.It will be greatly significant to clarify the pathogenesis of HCMV infection.

Objective:To investigate the effect of dexamethasone on the growth and the mechanism of apoptosis in K562 cells.Methods:Treat of different dosages of dexamethasone in K562 cell cultural to observe cell inhibitory rate and cell morphology variation.To detected telomerase activity,Fas expression and NO release.Results:Dexamethasone can inhibit the proliferation of K562 cell,decrease telomerase activity,increase Fas expression and induce apoptosis.But no significant effect on nitric oxide production.Conclusion:Inhibit telomerase activity and increase Fas expression maybe one of mechanism of apoptosis.

As an essential trace element for human,Zn is involved in the synthesis of various enzymes,and plays important roles in the growth and proliferation of cells.At the cellular level,Zn2+ homeostasis is maintained through the complex mechanisms of uptake,storage and excretion,where the Zn transporter families play certain roles.Two major Zn transporter families,namely the SLC30 (ZnT) family and the SLC39 (ZIP) family,have been identified,which act to control the intra-and extracellular equilibrium of Zn2+.While the ZnT family mainly transports Zn out of the cells,while the ZIP family mainly contributes to the uptake and transport of Zn into the cells.The ZIP family has been noted to be associated with various diseases,and be closely related to the development and progression of tumors.Recent studies have suggested low ZIP1 and ZIP2 expression in prostate cancer,high ZIP6,ZIP7 and ZIP10 expression in breast cancer,high ZIP3 and ZIP4 expression in pancreatic cancer,and high ZIP5 and ZIP6 expression in esophageal cancer.The ZIP family may,therefore,function as tumor suppressor genes in prostate cancer,and oncogenes in pancreatic cancer,breast cancer and esophageal cancer.This paper reviews the latest research progress on SLC39 transporter family and tumors.

Problem oriented system teaching method has been put into practice,and contrast has been made with traditional teaching method in the teaching of diagnostics in the technical secondary school of Chinese and western medicine special field.Result indicates that the improved teaching effect has been obtained and the students'initiatives and their ability to learn independently have been cultivated.

Objective To observe the therapeutic effect of recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)on osteoarthritis(OA)induced by sodium iodoacetate(MIA)in rats.Methods Female Wistar rats were divided into normal control group(11 rats)and model group(55 rats)according to the threshold of heat pain. After 3 d of modeling,the model group was randomly divided into solvent control model group(placebo),low-dose group(9 mg/kg rhIL-1Ra)and high-dose group(18 mg/kg rhIL-1Ra),with 12 rats in each group,according to the swelling rate of the left hindlimb knee joint,which were subcutaneously injected through neck,1 mL/kg once a day for 14 consecutive days. The diameter of the left hindlimb knee joint was measured 3 d before and after modeling and 2,4,7 and 14 d after the initial administration,and the swelling degree,swelling rate and swelling inhibition rate were calculated. The knee joint specimens of the left hindlimb were fixed,embedded in paraffin,sectioned,then stained with safranin O,and scored the pathological lesion under microscope.Results After 3 d of modeling,the swelling rates of knee joint of rats in all groups except normal control group reached about 30%. Compared with the solvent control model group,the swelling degree and swelling rate in the lowdose group decreased at both 2 and 4 d(1. 52 ± 0. 38 and 1. 26 ± 0. 43)(t = 1. 924,1. 945,each P < 0. 05)after administration,while those in the high-dose group all decreased significantly at 2,4 and 7 d(1. 51 ± 0. 37,1. 15 ± 0. 24,and1. 14 ± 0. 39)(t = 2. 976,2. 874,2. 902,each P < 0. 01). Compared with the solvent control model group,the degrees of articular cartilage lesions in the low and high dosage groups(8. 33 ± 1. 86,8. 17 ± 2. 79)were similar,and the statistical results of pathological scores showed a slight decrease(t = 1. 814,each P > 0. 05),indicating that the model was established successfully.Conclusion After 14 d of administration,high dose of rhIL-1Ra significantly reduced the knee joint swelling in acute stage of MIA-induced osteoarthritis in rats,but had no significant effect on the pain perception in MIAinduced chronic knee arthritis,and did not significantly reverse the knee cartilage injury induced by MIA.

Construction Materials ; Dust ; prevention & control ; Occupational Exposure ; prevention & control ; Ventilation ; instrumentation ; Workplace

Female ; Humans ; Leiomyomatosis ; diagnosis ; surgery ; Uterine Neoplasms ; diagnosis ; surgery ; Vascular Neoplasms ; diagnosis ; surgery ; Vascular Surgical Procedures ; methods ; Veins

Dopa-responsive dystonia(DRD) is a clinical syndrome characterized by childhood dystonia and dramatic and sustained response to low-dose levodopa.The deficiency of any link in dopamine synthesis pathway can lead to DRD that is caused by TH gene mutation and is autosomal recessive, which results in the reduction of tyrosine hydroxylase(TH) synthesis and extensive deficiency of dopamine and catecholamine.However, DRD presents atypical clinical manifestations.Mild patients mainly present with dystonia.Some of them might progressively develop into spastic paraplegia and some may have parkinsonian features.Most of them display good response to levodopa.Severe patients present with progressively complex infantile encephalopathy, and badly response to levodopa and remnant intellectual development problems.Most of them manifest with declining homovanillic acid(HVA) in cerebrospinal fluid.However, due to the noncharacteristic clinical course and nonspecific laboratory tests of TH DRD, gene detection still is the only reliable criterion of diagnosis so far.Low-dose levodopa is effective to most mild patients and can improve symptoms to severe patients to some extent.