1.Hypoxic preconditioning: effect, mechanism and clinical implication (Part 1).
Chinese Journal of Applied Physiology 2014;30(6):489-501
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
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Brain
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physiology
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Disease Models, Animal
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Hypoxia, Brain
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physiopathology
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Hypoxia-Inducible Factor 1
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Ischemic Preconditioning
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Mice
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Signal Transduction
2.Tumor Susceptibility and Digestic System Tumor Susceptible Gene
Basic & Clinical Medicine 1999;19(5):394-400
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.
3.Inguinal hernia and cord lipomas
International Journal of Surgery 2009;36(2):129-131
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.
4.Picture memory ability and related factors of the middle-aged and elderly population in Huaian city
Chinese Journal of Tissue Engineering Research 2005;9(20):235-237
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.
5.The relationship between femur and serum calcium and phosphorus content in osteoporosis
Journal of Chinese Physician 2011;13(1):58-60
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.
6.Spiral CT Diagnosis of Hypoxic Ischemic Encephalopathy in New Born(An Analysis of 114 Cases)
Journal of Practical Radiology 1992;0(11):-
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.
7.Effects of uric acid on TGF-?1 and Smad3 expression in human urethral fibroblasts
Journal of Third Military Medical University 2003;0(11):-
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
8.An Analysis of Low-field MRI in Early Stage of Cerebral Hemorrhage
Journal of Practical Radiology 2010;26(1):14-16,35
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.
9.Advances in the targeted therapy of cancer:multi-targeted Raf kinase inhibitor
China Oncology 1998;0(01):-
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.
10.MRI Diagnosis of the Pyogenic Infection in Gluteus Muscles
Journal of Practical Radiology 2000;0(12):-
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.