Osteoarthritis is one of the most common diseases seen in clinical practice. Cartilage survives in the hypoxic microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a key nuclear transcription factor which mediates the hypoxic response of cells. HIF-1α gene is an important regulator for the adaptation of articular cartilage to the hypoxic environment. It is important for formation of articular cartilage, energy metabolism and matrix synthesis. If the HIF-1α gene is knocked out, the cartilage can not maintain their normal morphology and function, which may lead to cartilage degeneration, and result in diseases such as osteoarthritis. Chinese herbal medicines can regulate the expression of HIF-1α gene and supply a therapy method for osteoarthritis. In this paper, the authors review the situation of the correlation between HIF-1α and osteoarthritis cartilage degeneration examined in recent years.

Objective To compare the short-term effect of Docetaxe and Irinotecan combined with Xeloda in treatment of end stage gastric cancer.Methods 65 patients with advanced gastric cancer were randomly divided into two groups.33 patients in group A received Docetaxe plus Xeloda and 32 patients in group B received Irinotecan plus Xeloda.At least two treatment cycles were completed.Results The overall response rate is 54.54%(A) and 53.13%(B),and the median progression-free survival was 6.1 months and 6.2 months.Patients in group A experienced more anemia,and patients in group B,diarrhoea.Conclusion The effects of Docetaxe or Irinotecan combined with Xeloda in the treatment of advanced gastric cancer are comparable and well tolerated.

Acute kidney injury (AKI) is a frequent syndrome in hospitalized patients .Recently, a number of studies have been reported that the close relationship exists between genetic polymorphism and AKI .The current research on genetic polymorphism related with AKI is reviewed in this article .

Objective To discuss the mechanism of large dose methylprednisolone(MP) on cerebral protection of rats after focal ischemic reperfusion.Methods Using the Wistar rat models of focal cerebral ischemic reperfusion,we observed the effects of large dose MP before and after ischemia on the volume of middle cerebral after infarction and the change of cerebral water content,meanwhile the pathological change of brain tissue was observed.Results Compared with the control group, the volume of middle cerebral after infarction in MD treatment group was remarkably reduced before and after ischemia (P 0 05 ). From the control group but not the MP treatment group, we found cerebral infiltration of macrophages from the histopathology of rat brain tissues.Conclusion Large dose MP might improve ischemic brain injury,the mechanism related to reducing volume of cerebral infarction and inhibited the infiltration of macrophages in the rat brain tissues.

The psychiatric problem has become a global public health issue. The model of mental health service advocate that“Treatment of disease occurred in the hospital, but rehabilitation and management in the community”. This brings great challenge to the community health service center. By comparing the domestic and foreign mental health service system, this paper discusses the necessity of carrying out the standardized training of general practitioners in psychiatry and psychology.

Objective:To evaluate the sealing ability of the 3.0th generation of polyamidoamine dendrimer(3.0 PAMAM)on hu-man dentinal tubules.Methods:1 6 extracted premolars were cut into 2 mm thick dentin slices to establish sensitive dentin model in vitro.Then 2 samples without any treatment were selected randomly into demineralized dentin group,and the remain 1 4 dentine pills were divided into 2 groups by the random number table(n=7).Samples in the experimental group were treated with 3.0 PAMAM, those in the control group were treated with deionized water.After having immersed in the artificial saliva for 2 and 4 weeks respec-tively,the dentin slices were examined by scanning electron microscope(SEM)and X-ray energy dispersive spectroscopy(EDS). Results:SEM showed that the minerals on the surfaces of the dentine disks in experimental group were formed gradually with the time,the dentinal tubules were blocked 4 weeks after treatment.The minerals on the sample surface in control group were less and the dentinal tubules remained open.EDS results showed that Ca/P(1 .49 ±0.1 6)of mineral deposition in the experimental group was higher than that in the control group (1 .1 8 ±0.20)(P<0.05).Conclusion:The 3.0th generation of PAMAMhas the occlu-ding ability by inducing remineralization on the dentine surface and it may be used in the treatment of dentin hypersensitivity.

[ ABSTRACT] AIM:To investigate the effect of paricalcitol ( P) on renal tubulointerstitial fibrosis and the under-lying mechanisms in diabetic nephropathy ( DN) .METHODS:DN rat model was induced by a single intraperitoneal in-jection of streptozotocin after fasting.The animals were randomly divided into 2 groups: the DN rats in paricalcitol-inter-vened group ( group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4μg/kg (3 times a week);the DN rats in DN group ( group D) were given isopyknic propylene glycol.Normal control group ( group C) was also set up.The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks.The biochemical indexes were measured.The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4,β-catenin and Klotho by immunohistochemistry and Western blotting.In addition, the correlation among the above indexes was analyzed.RESULTS:(1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D ( P<0.05 ) .( 2 ) The area of renal tubulointerstitial fibrosis in-creased in group D compared with group C, while decreased in group P compared with group D (P<0.05).(3) The ex-pression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05).Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 andβ-catenin decreased in group P (P<0.05).(4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 andβ-catenin (P<0.05).CONCLUSION:Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.

0.05).Again,compared with NG group,the protein expression of PKC? in HUVECs was up-regulated,the cytosol/nuclei ratio of PKC? was decreased,cell cycle was blocked in G0/G1 phase,the apoptosis increased significantly,and the protein content of p-FOXO1(S256) and P27kip1 increased(P

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.

ObjectiveTo study the effect of 1,25-(OH)2D3 analogs paricalcitol on proteinuriaindiabeticnephropathy (DN)rats, andtoinvestigateitspossiblemechanism.Methods DN model rats were established by intraperitoneal injection with streptozotocin.All the DN rats were randomly divided into the paricalcitol group(group P ) and DN group(group D).Healthy rats were chosen as healthy control group(group N).24-h urinary protein and serum biochemical indicators were examined after 12 weeks.ELISA was applied to detect the level of renin and Ang Ⅱ in the kidney.Immunohistochemistry and real-time PCR were used to detect the protein and mRNA expression of heparanases(HPA)and podoein.Results Compared with group N,24-h urinary protein,serum creatinine,renin and Ang Ⅱ in group D and group P were markedly increased,and they were significantly higher in group D as compared to group P (all P＜0.05).Compared with group N,the expression of HPA protein and mRNA in group D and group P increased markedly,and higher expression was found in group D(all P＜0.05).The expression of podocin protein and mRNA in group D and group P decreased markedly,and lower expression was found in group D(all P＜0.05).Renin level was positively correlated with HPA protein expression (r=0.78,P＜O.OS),negatively correlated with podocin protein expression(r=-0.63,P＜O.05),and not correlated with their mRNA expression.Conclusion Paricalcitol can significantly reduce the proteinuria,which may be associated with the inhibition of renin by down-regulating protein expression of HPAin glomerular basement membrane and up-regulating protein expression of podocin in podocyte.