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

The carcinogenesis and development is a progress of multi-gene alterations in the human gastric cancer (HGC)．In order to determine the relation between the aberration of these genes and gastric cancer，we chose c-met (7q31)、hMLH1 (3p21)、E-cadherin (16q22.1) and HLA loci DQA1、DR2、DR3、DR4、DR7、DR9 and detected their changes in 32 tumor specimens of intestinal type HGC and 4 cell lines of gastric cancer by performing analysis of SSP/PCR、PCR/SSCP and MSI technigues．Our data show that none point mutation was detected in c-met gene．We examined two microsatellites loci D3S1298 and D3S1561 in hMLH1 gene and detected that 6 cases retain MSI (Microsatellite Instability) and 2 cases of LOH (Loss of Heterozygosity) at D3S1298 and 2 cases of MSI at D3S1561．We also examined E-cadherin gene at two microsatellites loci D16S3083 and D16S3095 close to the gene and detected that 5 cases retain MSI and 1 case of LOH at D16S3083 and no change at D16S3095．The point mutation incidence of HLA-DR4 loci is 9/20 (45%)，higher than the other loci in HLA-Ⅱ．High frequent deletion，expression deregulation and methylation of mts1/p16 gene were detected in cell lines and solid tumors from human gastric cancer patients． 　　Our data showed that the point mutation of c-met gene is not the main pattern of alteration in intestinal type HGC that is consistent with the previous results．E-cadherin and hMLH1 are related to intestinal type HGC but whether they are susceptibility gene still need further study．The point mutation of the HLA-Ⅱ loci DR4 is closely related to intestinal type HGC．Methylation of mts1/p16 gene 5 CpG island might be plays an important role in the carcinogenesis in HGC．

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.

This article reported hospice care for a patient with pancreatic cancer in the end-of-life stage. We relieved the patient's pain and other painful symptoms,provided psy-chological counseling and support,respected the patient's wishes and autonomy,and guided family members to ef-fectively participate in end-of-life care. Through the above interventions,we attained the goal that the patient passed away peacefully and their caregivers lived without regrets.

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

Multi-drug resistance of breast cancer remains a major obstacle for effective treatment,which involves many complicated mechanisms,including drug transport in the body,metabolism and drug targets.Recent researches find that the tradition Chinese medicine not only has good effects in improving the body resistance and general situation of patients and enhancing the effects of chemoradiotherapy,but also plays a vital roles in the muti-drug resistance reversal of breast 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.

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 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 study the relationship between femur and serum calcium and phosphorus content in rat with osteoporosis. Methods We developed animal models with rat experienced bilateral oophorectomy and used inductively coupled plasma atomic emission spectrometry (ICP-AES) to determine calcium and phosphorus content in femur and serum of experimental group as well as control group. Results Calcium and phosphorus contents in femur in experimental group were significantly lower than that in control group[Ca: (218.59 ± 10.43) mg/L vs (253.32 ±7.54)mg/L;P:( 127.82 ±3.71 )mg/L vs ( 142. 18 ±5.99 ) mg/L, P ＜0. 01], but in serum experimental group it was significantly higher than that in control group [Ca: (99.45 ±0.76)mg/L vs (97.56±0.80) mg/L;P: (67.68 ± 1.63) mg/L vs (60.00 ± 1.18) mg/L,P ＜0. 01]. Conclusion Femur calcium and phosphorus levels were significantly reduced, which was related to the increase of serum calcium and phosphorus content, and it was one of the causes of osteoporosis.