Hypoxic preconditioning (HPC) refers to exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that is able to result in a resistance to subsequent severe hypoxia/ischemia in tissues and cells. The effects exerted by HPC are well documented. The original local in situ (LiHPC) is now broadened to remote ectopic organs-tissues (ReHPC) and extended crossly to cross pluripotential HPC(CpHPC) induced by a variety of stresses other than hypoxia/ischemia, including cancer, for example. We developed a unique animal model of repetitive autohypoxia in adult mice, and studied systematically on the effects and mechanisms of HPC on the model in our laboratory since the early 1960s. The tolerances to hypoxia and protection from injury increased significantly in this model. The adult mice behave like hypoxia-intolerant mammalian newborns and hypoxia-tolerant adult animals during their exposure to repetitive autohypoxia. The overall energy supply and demand decreased, the microorganization of the brain maintained and the spacial learning and memory ability improved but not impaired, the detrimental neurochemicals such as free radicals down-regulated and the beneficial neurochemicals such as adenosine(ADO) and antihypoxic gene(s)/factor(s) (AHGs/AHFs) up-regulated. Accordingly, we hypothesize that mechanisms for the tolerance/protective effects of HPC are fundamentally depending on energy saving and brain plasticity in particular. It is thought that these two major mechanisms are triggered by exposure to hypoxia/ischemia via oxygen sensing-transduction pathways and HIF-1 initiation cascades. We suggest that HPC is an intrinsic mechanism developed in biological evolution and is a novel potential strategy for fighting against hypoxia-ischemia and other stresses. Motivation of endogenous antihypoxic potential, activation of oxygen sensing--signal transduction systems and supplement of exogenous antihypoxic substances as well as development of HPC appliances and HPC medicines such as AHFs are encouraged based on our basic research on HPC. HPC may result in therapeutic augmentation of the endogenous cytoprotection in hypoxic-ischemic or suffering from other diseases' patients. Evolutionary consideration of HPC and clinical implications of HPC are both discussed to guide future research. The product of AHF is expected to be one of the most effective first aid medicines to rescue patients in critical condition. HPC is beginning to be used in surgery and is expected to be developed into a feasible adaptive medicine in the near future.
Animals ; Brain ; physiology ; Disease Models, Animal ; Hypoxia, Brain ; physiopathology ; Hypoxia-Inducible Factor 1 ; Ischemic Preconditioning ; Mice ; Signal Transduction

Animals ; Bilirubin ; toxicity ; Brain ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Rabbits

Objective To approach the characteristics of low-field MRI in early stage of cerebral hemorrhage.Methods 38 cases with early stage of cerebral hemorrhage (superacute stage in 26 and acute stage in 12) underwent low-field MRI examination.Results The hematomas located in the basal ganglia regions in 23,thalamus in 9 and other intracerebral regions in 6.The hematomas appeared as reniform,suborbicular or irregular shape with different size.The hematomas exhibited homogeneously iso-intensity on T_1WI and iso-,slightly high or high signal intensity on T_2WI and FLAIR,in which 5 hematomas exhibited iso- or slightly high signal intensity on T_2WI,and 4 hematomas exhibited homogeneously or inhomogeneously high signal intensity on DWI.There was brain edema around the hematomas.25 hematomas had occupied effect,and 4 hemotomas broke into ventriculus and 2 hemotomas caused by hemorrhage of broken arteriovenous malformation.Conclusion Low-field MRI is of high sensitivity and specificity in diagnosis of early stage of cerebral hemorrhage.

Objective To observe the effects of urine on TGF-?1 and Smad3 expression in cultured human urethral fibroblasts and explore the mechanism of urethral scar fibrosis.Methods The human urethral fibroblasts were cultured and stimulated by urine or 350 ?mol/L uric acid.The mRNA and protein expression of TGF-?1 and Smad3 were measured by PT-PCR and immunofluorescent staining,respectively.Collagen Ⅰlevels in the supernatants in different groups were detected by ELISA.Results TGF-?1 and Smad3 were detected in human urethral fibroblasts by immunofluorescent staining.After being presented with urine or uric acid at physiological concentration,both TGF-?1 and Smad3 in human urethral fibroblasts were increased significantly at both the protein and mRNA levels(P

Objective To analyze clinical and pathological characteristics of ocular malignant melanoma.Methods The tumor tissue specimens of 40 ocular malignant melanoma patients were given HMB-45,S-100 monoclonal antibody HE and immunohistochemical staining,and the general information of patients,tumor location,histologic type and prognosis were also analyzed.Results In the 40 patients,25 cases occurred in the uvea,ocular surface tissue in 8 cases,orbital secondary tumors in 4 cases,2 cases of eyelid,lacrimal sac in 1 case.Pathological typing:shuttle A cell type in 13 cases,B 12 cases,spindle cell type mixed cell type in 10 cases,epithelial cell type in 2 cases,3 cases of other types.In 40 patients with S-100 showed strong positive.HMB-45 was strongly positive in 20 cases,moderate positive in 18 cases,weakly positive in 2 cases.All patients were followed up for 2 years,the pathological type of diffusion or rewarming rate:shuttle A cell type 7.7％(1/13),shuttle B cell type 0.0％,mixed cell type 10％(1/10),epithelial cells of type 50％(1/2),other types 33.3％(1/3),other types and epithelial type tumor proliferation rate or relapse rate were significantly higher than other pathological types(x2=12.46,P＜0.05).＜50 years age group 28 cases,aged 50 years in 12 cases,the difference between the two groups was statistically significant(x2=12.80,P＜0.05);male 22 cases,female 18 cases,the difference was not statistically significant(x2=0.80,P＞0.05).Conclusion ocular malignant melanoma occurred in uveal and ocular surface tissue,spindle cell type is the most common,other types and epithelial cell type melanomas diffusion rate or a high recurrence rate,the disease with high degree of malignancy,should pay attention to its early diagnosis and treatment.

Objective To evaluate spiral CT in the diagnosis of hypoxic ischemic encephalopathy (HIE) in new born.Methods 114 cases HIE were examined with spiral CT, CT findings were analyzed.Results Brain edema of difference degree was found in all cases,thirty cases were showd intracranial hemorrhage.Conclusion Spiral CT scan is helpful for evaluating brain injury with HIE.

Objective To explore the applied value of MRI in diagnosing pyogenic of infection of gluteus muscles.Methods MRI data in 9 cases with pyogenic infection of gluteus muscles proved by operation or biopsy were retrospectively analysed by comparison with the pathological diagnosis.Results The pyogenic infections localized at unilateral gluteus muscles involving single,two or three gluteus muscles in all cases.On MRI,the infective gluteus muscles were swelling diffusely and the infections developed along the long axis of the muscles and most or all gluteus muscles were involved.4 cases appeared as suppurative myositis and 5 cases developed typical abscess.4 cases were accompanied with subcutaneous edema and the abscess broken into skin in one case.Conclusion The pathological characteristics of the stage and extent of the pyogenic infection in gluteus muscles can be displayed by MR imaging.

Advances in the understanding of cancer at the molecular level have led to much progress in the development of anti-cancer agents. Among the newly invented medications for targeted cancer therapy, protein kinase inhibitors target intracellular molecules crucial in signaling pathways for cancer cell survival, proliferation, and disease progression. The Raf serine/threonine kinases are pivotal molecules within the Raf/mitogen extracellular kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. The exact function of Raf in normal human cells is not yet understood; however, preclinical and clinical researches have shown that over expression of Raf gene or overreaction of Raf kinase isoforms have critical roles in many types of solid tumors, including renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer (NSCLC). Sorafenib is the first oral, multi-kinase inhibitor that targets the Raf kinases. It also has a broad spectrum activity against other receptor tyrosine kinases associated with vascular endothelial growth factor receptors and platelet-derived growth factor receptors. Sorafenib was recently approved by FDA for use in advanced renal cell cancer, and is currently undergoing active investigation in the treatment of other types of malignancies, such as melanoma, liver cancer, prostate cancer, and NSCLC. In this review, we will illustrate the role of Raf in both normal and malignant cells, the mechanism of sorafenib in the treatment of renal cell carcinoma, as well as clinical data that support its use and further investigation in advanced renal cell carcinoma, melanoma, and other tumor types.

Background Studies showed that vascular endothelial growth factor (VEGF) plays an important role in the development and progress of diabetic retinopathy (DR),and the association between VEGF-2578C/A polymorphism(SNPs) and risk for DR is a hotspot.Objective This Meta analysis aimed to investigate the comprehensive and reliable conclusion in the association of VEGF-2578C/A SNPs and risk for DR in different races.Methods A systematic search of electronic databases including PubMed,Cochrane Library,EMbase,VIP,Wanfang technological,CNKI and reference lists of relevant articles was carried out until April,2014.Case-control studies on the relationship between VEGF-2578C/A SNPs and DR were selected based on inclusion and exclusion criteria,and the relevance of VEGF-2578C allele to DR,the relevance of VEGF-2578C/A SNPs to DR and the relevance of VEGF-2578A allele to Caucasian DR were quantitatively analyzed.Begger funnel plot of publication biases on the relationships of VEGF SNPs with the risk of DR under the allele and dominant models was drown.RevMan 5.0 software was used for the statistical analysis.The pooled odds ratio (OR) and corresponding 95％ confidence interval (CI) were used to assess the strength of the association.Results A total of 1 228 DR cases and 1 224 diabetes controls without retinopathy(DWR) were included from 8 independent studies (9 groups of data).A significant relationships between VEGF-2578A allelic gene and VEGF-2578AA gene type with DR were found in all samples,and the A allelic gene and AA gene type were the risk genes of DR (A versus C:OR=1.39,95％ CI=1.08-1.80,Z=2.52,P=0.01;AA versus CC+C/A:OR=1.53,95％ CI=1.05-2.24,Z=2.20,P=0.03;CC versus AA+C/A:OR=0.70,95％ CI=0.50-0.98,Z =2.10,P =0.04).When the other two studies which did not meet the HardyWeinberg Equilibrium were incorporated in a sensitivity analysis,the results were not materially altered.VEGF-2578 A allelic gene was the risk gene to Europeans with DR (OR =1.50,95％ CI=1.02-2.21,Z =2.07,P =0.04),but not among Asians in subgroup analysis (P＞0.05).No significant publication bias was found.Conclusions The Meta analysis demonstrates that VEGF-2578C/A is associated with DR in Europeans but not in Asians.Further case-control studies based on larger sample size are still needed,especially in Asians.

Objective To investigate the effects of p53 on expression and activity of protein kinase R (PKR) as well as biological characters of HeLa cells from cervical carcinoma patients. Methods Recombinant plasmid vector pEGFP-C1/p53 was constructed to over-express p53 then it was transfected into HeLa cells. Transcription levels of p53 and PKR mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR) among pEGFP-C1/p53 transfection group, pEGFP-C1 transfection group and blank control group(only transfection reagent was added);Protein expression lev?els of p53, PKR, phosphated PKR(p-PKR)and phosphatedαsubunit of eukaryotic initiation factor 2(p-eIF2α)which is the downstream substrate of PKR were detected by Western Blot among three groups;Proliferation of HeLa cell were deter?mined by methyl thiazolyl tetrazolium(MTT)assay;Invasion of HeLa cell were determined by Transwell cell assay. Re?sults Recombinant plasmid vector pEGFP-C1/p53 was successfully constructed to overexpress p53;Transcription level of p53 and PKR mRNA in pEGFP-C1/p53 transfection group were higher than those in pEGFP-C1 transfection group and in blank control group (P<0.05),and there were no significant difference between their levels in pEGFP-C1 transfection group and in blank control group;Protein expression levels of p53, PKR, p-PKR andp-eIF2α in pEGFP-C1/p53 transfection group were higher than those in pEGFP-C1 transfection group and in blank control group (P<0.05),and there were no sig?nificant difference between those expression levels in pEGFP-C1 transfection group and in blank control group;MTT and Transwell cell results showed that proliferation and invasion of HeLa cells in pEGFP-C1/p53 transfection group were weaker than those in pEGFP-C1 transfection group and in blank control group (P<0.05),and there were no significant difference between proliferation and invasion of HeLa cells in pEGFP-C1 transfection group and in blank control group. Conclu?sion p53 can up-regulate the expression and activity of PKR, promote activation of PKR/eIF2αsignal transduction pas?sage and restrain cell proliferation and invasion of HeLa cells.