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

BACKGROUND:Human memory is significantly correlated with recognition. When recognition begins to decrease, a decrease in memory appears first. How about the memory of rural population?OBJECTIVE:To investigate the picture memory related factors of the rural households who are over 50 years old.SETTING:Department of Geriatrics,Huaian First Hospital,Nanjing Medical University;Department of Neurology, Huashan Hospital,Fudan University.PARTICIPANTS:Totally 50 rural inpatients at the Department of Geriatrics,Huaian First Hospital Nanjing Medical University,who would be recovered and out of charge,were selected from March 2003 to February2004. Meanwhile, 11 relatives of the patients and 55 healthy elderly people from Dingji Town,Huaiyin District, were also included.All the participants were over 50 years old.METHODS:Employing questionnaire,mini-mental state examination,auditory-verbal learning test (AVLT), pictorial learning test and many nonmemory tests were performed. According to the levels of education,participants were divided into illiterate group,primary school group,junior middle school group and higher than junior middle school group.The correlation of picture memory ability with sex,age,educational level and simple intelligence test was compared. And the interactions among variables of picture memory were also investigated.MAIN OUTCOME MEASURES:The relationships between the variablesof picture memory and age, sex, educational level and simple intelligence of rural households in Huaian city were calculated. And the interactions among these variables were all investigated.RESULTS:Practically, 103 participants entered the statistical analysis proage,sex,educational level and simple intelligence:Except for recurring figures, all the other variables of picture memory had positive correlations with simple intelligence and educational level (r=0.197-0.533, P ＜ 0.05-0.01).Among them, immediate memory showed the closest correlation with simple intelligence (r=0.533).Delayed recall memory of pictures, recurring figures,and serial memory 4 (the number of recalled pictures in the last 4 pictures in delayed recall test) had negative correlation with age (r=-0.194 to -0.324,P ＜ 0.05-0.01),among them, serial memory of 4 pictures had the closest correlation with age (r=-0.324),while, all the other variables were not related to age. All the variables of picture memory were not linked to sex. Recurring pictures was not linked to educational level 1 (period of education:0-11 years),2 (education level: illiterate, primary school, junior middle interactions among these variables:Recurring figures was not linked to serial memory 2 (the number of recalled pictures in the last 4 pictures in immediate memory test),serial memory 1 (the number of recalled pictures in the first4 pictures in immediate memory test) was not related to serial memory 2 and serial memory 4.Except for these cases, variables of picture memory had significant correlations with each other (r =0.206-0.855 ,P ＜ 0.05-0.01),and delayed recall memory of pictures had the closest relationship with conceptual memory 2 (r=0.855).CONCLUSION:Picture memory capacity of middle aged and elderly rural households is not linked to sex, while it is correlated with age,educational level and intelligence.

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.

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.

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.

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.

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.

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