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

Public hospital reform pilots have been initiated recently and it is necessary to clarify some key issues. To this end, thispaper touches upon six fundamental issues, discussing the generality and value for the existence of public hospitals, differences between reforms of public hospital and those of state-owned enterprise, the public financing for and regulation on public hospitals, relationship with the private sector, as well as service and function positioning of public hospitals.

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

The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.
Amygdalin ; pharmacology ; Animals ; Apoptosis ; Cells, Cultured ; Chalcone ; analogs & derivatives ; pharmacology ; Chondrocytes ; drug effects ; Collagen ; metabolism ; Drug Synergism ; Interleukin-1beta ; Intervertebral Disc ; cytology ; Quinones ; pharmacology ; Rats

Objective To investigate the potential relationship between initial 131Ⅰ uptake by lung metastases from differentiated thyroid cancer (DTC) and treatment outcomes. Methods From 1997 to 2009, 41 patients with DTC lung metastases were treated in the authors' department. 131Ⅰ whole body scan (WBS), serum Tg levels and other imaging results were analyzed to evaluate the therapeutic effects. Complete response (CR) or partial response (PR) was considered to be effective. The x2 test and correlation analysis were performed using SPSS 11.5 software package. Results 131 Ⅰ treatment was effective in 63% (26/41) patients with DTC lung metastases, CR in 8 patients and PR in 18 patients. In other 37% ( 15/41 ) patients, 131Ⅰ treatment was ineffective, including one case died of distant metastases. Patients with initial presence of 131Ⅰ lung uptake had higher effective rate than those with 131Ⅰ lung uptake during the second or later 131Ⅰ treatment (76% (22/29)vs33% (4/12),x2 =4.911, P=0.027). Also, significantly higher effective rate was found in patients with lung metastases alone than those with extra-pulmonary metastases (75% (24/32) vs 22% (2/9), x2 = 6. 312, P =0.012). However, the effective rate in patients with diffuse metastases was not significantly different from that in patients with focal metastases (67% (12/18)vs 61% ( 14/23), x2 =0. 146, P=0.702). The positive rate of initial 131Ⅰ uptake by lung metastases was higher in patients with total thyroidectomy than those with partial thyroidectomy (83% (24/29) vs 42% (5/12) ). Those positive rates in patients with papilary DTC and patients with follicular DTC were 72% (23/32) and 6/9, respectively. The surgical mode was correlated with the initial 131Ⅰ uptake by lung metastases (r = 0.411, P ＜ 0.05), but no correlation was found between the histological type and the initial 131Ⅰ uptake by lung metastases ( r = 0. 047, P ＞ 0.05 ). Conclusion Initial uptake of 131 Ⅰ by lung metastases alone is a favorable prognostic factor for DTC patients treated by131Ⅰ, and total thyroidectomy may be beneficial for initial 131Ⅰ uptake by lung metastases.

Objective To investigate the function of transferrin-DNA complex,transported by transferrin(Tf)and trans-arterial injection via interventional approach be the duel-target-orientated delivery and the transferring into malignant cells to get more effective therapy.Methods p53-LipofectAMINE ligand with different concentrations of Tf(0,10,25,50,100?g)transfected the 4 strains including LM6、Hep3B、YY and L02 in vitro to evaluate the gene transfeetion efficiency through western blot.Then,after setting up the VX2 hepatocarcinoma models,we delivered the Tf-p53-LipofeetAMINE complex into the hepatic arteries via interventional techniques to analyse the transfection efficiency in vivo.Results Tf,within the range of 10 100?g,could increase gene transfection efficiency mediated by liposome,and the efficiency increases with the raise of Tf concentration.Combination with interventional technique to inject Tf-DNA complex into tumor arteries,gene transfeetion efficiency was enhanced in rabbit models.Conclusion Tf can enhance gene- liposome transfection efficiency,furthermore with combination of interventional catheter technique,there would be a potential duel-target-orientated gene therapy method.(J Intervent Radiol,2007,16:99-103)

This paper aimed to study the effect nitrogen supplying on biomass accumulation and root respiration dynamic change of Glycyrrhiza uralensis and reveal the metabolic pathway of root respiration impact the biomass accumulating of G. uralensis. Six groups of one-year-old G. uralensis were fertilized with total nutrition containing various nitrogen concentration (0, 0.5, 1, 2, 4, 8 mmol x L(-1)) every week. At the end of every month, from June to October, the volume respiration rate and biomass of different classes of root samples were determined, and the correlation between root respiration and biomass was analyzed. The results indicated a negative correlation between volume respiration rate and biomass, nitrogen supply significantly affected both root respiration and biomass of G. uralensis by reducing root respiration and increasing root biomass. Under 8 mmol x L(-1) nitrogen supplying, there existed the optimal inhibition of root respiration, which has increased biomass of G. uralensis.
Biomass ; Dose-Response Relationship, Drug ; Glycyrrhiza uralensis ; drug effects ; growth & development ; metabolism ; Kinetics ; Nitrogen ; pharmacology ; Oxygen Consumption ; drug effects ; Plant Roots ; drug effects ; metabolism ; Seasons ; Time Factors

OBJECTIVETo investigate the relationship between lumbosacral transitional vertebra and the lumbar disc herniation (LDH).

METHODSThe X-ray photographs of lumbar vertebra were retrospectively studied of patients with and without LDH confirmed by surgery, furthermore, the differential incidence of LDH between the two groups and the relationship between transitional vertebra and the position of disc herniation were statistically analyzed.

RESULTSThe incidence of lumbosacral transitional vertebra was 18.3% in the control group, 52.7% in the LDH group, the difference was statistically significant. In the group with single lumbosacral transitional vertebra, there was 75.9% of LDH occurred on the same side of the transitional vertebra, 81.8% of which occurred at the upper one disc of the transitional vertebra; whereas 17.2% of LDH on the opposite side of the transitional vertebra, 80.0% of which occurred at the lower one disc of the transitional vertebra.

CONCLUSIONSThere is a closer relationship between lumbosacral transitional vertebra and the LDH, and the lumbosacral transitional vertebra is one of the important factors in the emergence of LDH.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Intervertebral Disc Displacement ; etiology ; Lumbar Vertebrae ; diagnostic imaging ; Male ; Middle Aged ; Radiography ; Sacrum ; diagnostic imaging ; Spondylolisthesis ; complications

OBJECTIVE: To compare the outcomes of endoscopic combined ultrasound-guided access (EUGA) with the conventional ultrasound-guided access (UGA) to achieve percutaneous renal access in endoscopic combined intrarenal surgery (ECIRS). METHODS: A retrospective review of 53 patients undergoing ECIRS to treat upper urinary tract calculi between January 2017 and October 2019 was con-ducted. All of the cases were of complex upper urinary tract stones larger than 2 cm in diameter. The com-plex stone situations, such as multiple renal calyces calculi or staghorn calculi necessitated ECIRS. Under general anesthesia, the patients were placed in the galdakao-modified supine valdivia (GMSV) position, thus allowing both antegrade and retrograde accesss. The patients were divided to UGA and EUGA groups according to the protocol of achieving percutaneous renal access. In 28 cases, endoscopic combined ultrasound-guided accesss were obtained. Puncture and dilation were performed under direct flexible ureteroscopic visualization, while percutaneous renal access of 25 cases were performed with the conventional technique employing ultrasound guidance. Demographic and perioperative information, such as stone burden, presence of hydronephrosis and number of calyces involved was compared. Primary outcomes included total operative time, renal access time, repeat puncture, hemoglobin level, perioperative complications, and stone-free rate. RESULTS: No major intra-operative complication was recorded in all the 53 ECRIS. No significant difference was observed between the groups in age and gender. There was no significant difference in body mass index[BMI (29.21±3.14) kg/m² vs.(28.53±2.56) kg/m²], stone burden (37.68±6.89) mm vs. (35.53±6.52) mm, number of calyces involved 2.72±0.68 vs. 2.86±0.71, presence of hydronephrosis (56.0% vs. 46.4%), total operative time (93.0±12.2) min vs. (96.8±14.2) min, hemoglobin level reduction (6.56±2.16) g/L vs. 97.54±2.64) g/L, stone-free rate (92.0% vs. 92.8%), hospital stay (5.52±0.59) d vs. (5.64±0.62) d, perioperative complication rate (8.0% vs. 7.2%). Two patients in EUGA group experienced perioperative complications (one urinary tract infection and one hematuria) while two patients in UGA group experienced perioperative urinary tract infection. None in both groups received blood transfusion. The patients undergoing EUGA had shorter renal access time [(4.0±0.7) min vs. (6.8±2.6) min, P < 0.01] and less repeat puncture (0 vs. 4 cases, P < 0.05). CONCLUSION EUGA is an optimal technique to establish percutaneous renal access in ECIRS, which minimizes access time and repeated procedures.
Humans ; Kidney Calculi ; Nephrostomy, Percutaneous ; Retrospective Studies ; Treatment Outcome ; Ultrasonography, Interventional ; Ureteroscopy

Cadherins ; metabolism ; Female ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells ; metabolism ; Receptor, Notch1 ; metabolism ; Receptors, CXCR4 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor C ; metabolism