Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death ; Humans ; Hypoxia-Inducible Factor 1 ; antagonists & inhibitors ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Neoplasms ; drug therapy ; Oxygen ; metabolism ; Signal Transduction

Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.

Objective:To investigate the relationship between primary resection and KRAS gene mutation in the mild symptomatic patients with stage Ⅳ colorectal cancer,and to clarify its significance of prognosis.Methods:The clinical data of 46 mild symptomatic patients with stage Ⅳ colorectal cancer 2010 to December 2010 were collected.All the patients received primary resection.The KRAS gene mutation in the patients was detected by direct sequencing and the patients were followed up for 5 years.The influence of primary resection and KRAS gene mutation in prognosis of the patients with stage Ⅳ colorectal cancer was analyzed, and the clinical pathological features which might influence the prognosis were analyzed by survival analysis.Results:In 46 patients with colorectal cancer, KRAS gene mutation was found in 20 cases, the mutation rate was 43.4%, and most mutation was found at Codon 12. The KRAS mutation had relationship with the tumor site and multiple metastasis (P<0.05).The Kaplan-Meier survival curve and univariate analysis results showed that the median survival time of the patients with wild type of KRAS gene was 58.4 months, the median survival time of the patients with mutant type of KRAS gene was 42.2 months, and there was no significant difference (P>0.05).The median survival time of right colon cancer patients was 34.2 months, the median survival time of left colon cancer patients was 58.3 months, and there was sigificant difference (P<0.05).The cancer metastases including liver, lung and multiple metastasis were closely related to the poor prognosis of the colorectal cancer patients(P<0.05).The median survival time of the patients with stage Ⅳ colorectal cancer was 39.6 months after operation.Conclusion:After primary resection of the mild symptomatic patients with stage Ⅳ colorectal cancer,the median survival time of the patients with colorectal cancer in left colon site and right colon site were prolonged.Right colon cancer has more poorer prognosis than left colon cancer.KRAS gene mutation is associated with the tumor site and the multiple metastasis.The location of metastasis affect the prognosis.

Objective To investigate intradermal injection and subcutaneous injection of Gadodiamide MR lymphangiography (MRL) in evaluation on the central conducting lymphatics in rabbits.Methods T1 weighted three-dimendional fast low angle shot (fl3d) sequence was used before and after administration of Gadodiamide to undertake MRL.Gadodiamide was administed intrademally in the left and right footpad in 8 rabbits,and then undertake MRL in 1.5T MRI system (intradermal injection group).Three days later,Gadodiamide was administered subcutaneously in the left and right footpad in 8 rabbits,and MRL were underdone with the same sequence (subcutaneous injection group).The degree of contrast enhancement within the lumbar lymphatic trunk and thoracic duct were evaluated using a 3-point scoring system.Results Intradermal injection group showed the popliteal lymph nodes,sacral lymph node and inferior aortic lymph node enhanced obviously in all 8 rabbits,and the enhancement duration time was about 30 90 mini the lumbar lymphatic trunk and cisterna chyli were detected in 6 rabbits,and part of the thoracic duct were detected in 5 rabbits.Subcutaneous injection group showed the popliteal lymph nodes enhanced obviously in all 8 rabbits,but the lumbar lymphatic trunk and the thoracic duct were not detected.The score of contrast enhancement within the lymphatic system of intradermal injection group and subcutaneous injection group had statistical difference (t=100.00,P=0.0002).Conclusion MRL with intradermal injection Gadodiamide are better than subcutaneous injection in evaluation of the lumbar lymphatic trunk.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Objective To explore the the analytical method for the quality difference of Radix Salviae Mihiorrhizae (RSM) injection. Methods Parallel intercomparison experiment was carried out in different batches of RSM injection samples which had different degrees of adverse drug reaction. The samples were analyzed by gel size exclusion chromatog-zraphy and C18 HPLC fingerprint. Subtractive analysis was used to reveal the information of the non-low molecular weight phenolic acids. Results There were obvious differences between the results of size exclusion chromatography. The amount of the non-low molecular weight phenolic acids from different batches of the samples was also different, which was correlated with the degrees of acute toxicity in guinea pigs. Conclusion The amount of the non-low molecular weight phenolic acids varies with different batches of Radix Salviae Mihiorrhizae injection. It is suggested that non-low molecular weight phenolic acids can be used for the quality control of Radix Salviae Mihiorrhizae injection. For the first time, the perspective that the corresponding relationship between the fingerprint and their toxicities of Traditional Chinese medicine injection may be one of the most important fields is put forward.

ObjectiveTo probe the effect of the electroacupuncture on vascular dementia(VD) and content of arginine vasopressin(AVP) in brain of rats. Methods30 Sprague Dawley rats were made renal hypertension(RHR) by the kidney arteries pinched with silver clip.After 42 days, their bilateral common carotid arteries were blocked repeatedly to cause cerebral ischemia.The Hypertension Vascular Dementia model was made. Then they were divided into model group,electroacupuncture group and medicine group(Dihydroergotoxine,DHET) with 10 in each group. The course was 28 days. The ability of learning and memorizing was observed by water maze, and the content of AVP in brain was detected after treatment. ResultsThe latent period of the electroacupuncture group and medicine group was shorter than that of the model group(P<0.05-0.005), and that of the electroacupuncture group was shorter than medicine group(P<0.05-0.005). In frontal lobe, the contents of AVP in the electroacupuncture and medicine groups were higher than that of model group( P<0.01,P<0.05), and the electroacupuncture group was higher than medicine group in striatum (P<0.05). Conclusions It indicated that electroacupuncture therapy can promote the ability of learning and memorizing and enhance the content of AVP in the brain of VD rats. It's therapeutic effect is better than that of DHET.

Objective:To investigate the role of Th1/Th2 shift in unexplained recurrent spontaneous abortion (URSA) and to study the effect and molecular mechanism of Bushen Guchong decoction on URSA treatment by regulating Th 1/Th2 paradigm.Methods:30 cases of URSA patients were given Bushen Guchong decoction administration ; meanwhile,30 cases of normal pregnancy women were taken as control group.Th1/Th2 paradigm in peripheral blood monocytes of URSA patients before and after Bushen Guchong decoction administration was detected by flow cytometry.Moreover,the mRNA expression of the specific transcription factors for Th1 and Th2 subsets -T-bet and GATA-3 were detected by RT-PCR assay.Furthermore,the relationship between the Th1/Th2 paradigm and the uterine bleeding time after Bushen Guchong decoction administration was analyzed by Pearson correlation and re -gression tests.Results: Compared with normal pregnancy women , the proportion of Th1 subset of URSA patients was increased significantly (P<0.05),while the proportion of Th2 subset was decreased markedly (P<0.05).Additionally,the ration of Th1/Th2 subsets was increased in URSA women (P<0.05).After Bushen Guchong decoction treatment ,the proportion of Th1 subsets in URSA patients and T-bet mRNA expression were up-regulated significantly ( P<0.05 ) , whereas the Th2 proportion and GATA-3 mRNA expression were down-regulated obviously (P<0.05).Moreover,the ratio of Th1/Th2 was decreased significantly (P<0.05).Correlation analysis showed that the uterine bleeding time was positively related to both the proportion of Th 1 and the ratio of Th1/Th2, while negatively related to the proportion of Th 2 subsets.Conclusion:Th1/Th2 shift was involved in URSA.Bushen Guchong decoction up-regulated the transcription level of GATA-3 and down-regulated the transcription level of T-bet.Thereby, Bushen Guchong decoction exerted the curative effect on URSA by revising Th 1/Th2 shift.

Objective To investigate the effect of health education for discharged patients, and to explore the reasons and effective countermeasures on the health education. Methods Through the question-naire survey, convenient sampling method was used to evaluate the effect of the hospital health education. The existing problems and corresponding countermeasures taken for continuous improvement were analyzed. SPSS 17.0 statistical software was applied for data processing, the count data was expressed by rate and Statistical methods using chi-square test. Results The hospital health education satisfaction rate rose to 95.21%from 54.17%after intervention, and differences between the two groups was statistically significant (P<0.05). The satisfaction rate of the department of internal medicine, surgery department, and the department of gynaecology and pediatrics was significantly improved than before. Conclusion By improving health education importance, strengthening learning and training of specialized subject knowledge, rationally allo-cating human resources and establishing health education quality control system, the health education for discharged patients was effectively improved with satisfaction.

Objective To analyze the patterns of cortical atrophy of the two subtypes of frontotemporal lobar degeneration (FTLD ),behavioural-vsriant frontotemporal dementia (bvFTD ) and primary progressive aphasia (PPA).And to compare them with that of Alzheimer disease (AD) to provide an objective basis for early diagnosis and differential diagnosis.MethodsA total of 83 patients were enrolled in this study and there were 30 patients with cognitively normal controls (CN),30 with AD and 23 with FTLD (10 with bvFTD,13 with PPA).Philips 3.0 T TX scanner and 8 channel head coil was employed.Three dimensional turbo fast echo(3D-TFE)T1WI sequence with high resolution was used to collect the volume data of gray matter.3D-TFE T1 WI images were normalized and segmented into gray matter map for statistical analysis by SPM 8 and VBM 8.The false discovery rate (FDR) was adopted in P value adjustment,P ＜ 0.001,and the cluster size was set at 5.The full width at half maximum (FWHM ) was set at 4 mm for the smoothing.Paired t test was used for statistics.ResultsIn bvFTD,PPA and AD groups,there were diffuse regions with reduced volume in cerebral cortex and subcortical structures (such as the hippocampus,the amygdala,the caudate nuclei,et al).The most obvious atrophic region in bvFTD and PPA group was found in the frontotemporal.Compared with AD,gray matter atrophy in bvFTD was found in brain regions including bilateral temporal lobes,bilateral superior temporal pole gyri,bilateral middle temporal pole gyri,right fusiform gyrus and bilateral frontal lobes.Among them,temporal and frontal lobes atrophy had obvious right partial lateralizing,with 14 301 voxels in right temporal lobe and 5105 in left (t =-5.03,P＜0.05).The number of atrophy voxels in right and left frontal lobe were 1344 and 125 (t =3.45,P ＜0.05).The left temporooccipital lobe atrophy was more obvious than the right in PPA,with 15 637 voxels in left and 10 723 in right ( t =- 2.65,P ＜ 0.05 ).ConclusionsThere are different brain gray matter atrophy patterns in bvFD,PPA and AD.Among them,bvFTD has asymmetric right frontal and temporal lobe atrophy,which may be related to characteristic personality changes.On the other hand,the asymmetric atrophy in left temporooccipital lobe may be responsible for the aphasis of patients with PPA.