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

Objective To assess the association of vascular endothelial growth factor (VEGF) gene-460C/T and-634C/G polymorphism with diabetic retinopathy (DR) among patients in Asia and European by meta-analysis.Methods A systematic search of electronic databases (PubMed,Cochrane Library,EMBASE,VIP,Wanfang technological,CNKI,etc.) was carried out until Jun,2014.Case-control studies on the relationship between genetic polymorphism of VEGF-460C/T and VEGF-634C/G with diabetic retinopathy were included in this analysis.The data were quantitatively analyzed by RevMan 5.0 software after assessing the quality of included studies.The pooled odds ratios (OR) and their corresponding 95％ confidence intervals (CI) were used to assess the strength of the association.Results VEGF-460C/T (7 studies:899 cases and 786 controls) and VEGF-634C/G (10 studies:1615 cases and 1861 controls) were inclued in this meta-analysis.Significant association was found for-460C/T polymorphism in Aisa (C versus T:OR=1.52,95％CI was [1.22,1.90],Z=3.72,P=0.0002;CC versus CT+TT:OR=1.61,95％CI was [1.19,2.19],Z=3.05,P=0.002;TT versus CT+CC:OR=0.64,95％CI was [0.41,0.98],Z=2.07,P=0.04),and VEGF-634CC gene type was associated with DR in European (OR=1.56,95％CI [1.08,2.25],Z=2.37,P=0.02).No significant publication bias was found.Conclusions The metaanalysis demonstrated that DR was associated with VEGF-460C/T polymorphism in Asia,and C alleles and CC gene type was the risk polymorphism;VEGF-634C/G polymorphism was not associated with DR,but its CC genotype maybe the risk factor in European.Further case-control studies based on larger sample size are still needed,especially for-634C/G polymorphism.

Objective To identify the significance of expression and phosphorylation of protein kinase R(PKR) and nuclear factor NF-κB p65 in cervical lesions, and the effect of high-risk human papilloma virus(hsHPV) on expression and phosphorylation of R(PKR) and NF-κB p65. Methods A total of 67 patients with cervical cancer, 149 patients with cervi-cal intraepithelial neoplasia (CINⅠ-Ⅲ) and 15 normal control were included in this study. The expression levels of PKR, phosphorylated PKR (p-PKR), NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by immunohisto-chemical SP method in three groups. Results The positive expression rates of PKR and p-PKR in cytoplasm were signifi-cantly lower in hsHPV positive group than those in hsHPV negative group (27.2% and 11.0% vs 41.1% and 21.1%,χ2 =4.858 and 4.371,P＜0.05). The positive expression rates of NF-κB p65 and p-NF-κB p65 in cytoplasm and nucleus were significantly higher in hsHPV positive group than those in hsHPV negative group (46.3%, 25.7%, 22.8% and 12.5% vs 32.6%, 14.7%, 11.6%and 4.2%,χ2=4.345,4.048,4.729 and 4.650 respectively,P＜0.05). The positive expression rates of PKR in kytoplasm and karyon were significantly lower in NF-κB p65 (+) group than those in NF-κB p65 (-) group (25.5%vs 38.0%and 20.4%vs 36.3%,χ2=3.898 and 4.396 respectively, P＜0.05). The positive expression rate of PKR in kyto-plasm was significantly lower in p-NF-κB p65 (+) group than those in p-NF-κB p65 (-) group (19.0%vs 36.0%,χ2=4.462, P＜0.05). Conclusion hsHPV may inhibit the expression and phosphorylation of PKR but promote the expression and phosphorylation of NF-κB p65. The expression and phosphorylation of NF-κB p65 may inhibit the expression of PKR. Regu-lating effects of three may be associated with the generation and progression of cervical cancer.

Carcinogenesis is a multistep process that a couple of genes involve in the initiation of this disease.As a pivotal hallmark of cancer, the genomic instability ensues in which genetic alterations when this process was initialized and developed. With the increasing number of studies on genomic instability, the scientists pay more attentions on its biological function at post-genomic era. Genomic instability in various carcinomas is associated with broken telomere, gene modification, and contributes to the dysfunction of DNA damage and repair pathways.This review focus on the factors involved in genomic instability, as well the current detection methods of genomic instability and their clinical application.

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.

The paper is to investigate eco-design flaws in equipments for medical simulation training and explore methods to improve. The eco-design flaws in equipments for medical simulation training were elaborated from the aspects of accessories, modules, model volumes, recycling of waste equipments, and production materials. The improved methods of the flaws were demonstrated. The designs of equipments for medical simulation training can be more environment friendly by means of getting rid of unnecessary accessories, developing replaceable modules for manikin models, curtailing volumes of equipments, recycling waste equipment and using degradable production materials. As the tendency of being environment friendly in medical equipments becomes increasingly obvious, the eco-friend merits must be considered by multi-objective optimizations in the processes of design, manufacture, and employment of equipments for medical simulation training.

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.

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.

AIM: To study whether the excitatory amino acids (EAAs)-triggered excitotoxicity contribute to the evolution of hyperbilirubinemia-associated brain injury. METHODS: Newborn rabbits with hyperbilirubinemia were decapitated and then, Na~+-K~+-ATPase activities, neurotransmitters and non-neurotransmitters concentration in brains were determined. RESULTS: It was found that the activities of Na~+-K~+-ATPase both in brains and cytomembrane and the amounts of glutamate (P

Cord lipoma is a trite lipoma, it is a protrusion of extraperitoneal fatty tissue through the internal inguinal ring. The incidence is between 20% to 30%.It is often caused by a protrusion of extraperitoneal fatty tissue through the internal inguinal ring, lobular retroperitoneal fat insinuates itself through the internal ring and over time dilates it. Patients with a higher BMI are more prone to having a cord lipoma. Incidence of lipoma associated with Type II and Ⅲ hernias was bigher. it is suggest that the incidence of lipoma assoeiated with the type of hernias and patients with a larger hernias are more prone to having a coM lipoma. The cord lipoma is difficult to diagnosis before surgery,because it is similar to hernias in symptom. Ultrasound is safe and useful in finding hernias and cord lipoms, the overall accuracy is 92%. It is necessary to resect lipomas and repair as long as the extraperitoneal fatty tissue through into the inguinal canal.