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.

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.

Objective To evaluate the surgical technique in ventricular septal defect(VSD)associated with aortic valve insufficiency(AI)patients.Methods 115 VSD patients associated with AI were retrospectively analyzed.96 patients belong subarterial to VSD,membranous defect in 19 cases.Moderate hypothermia circulatory arrest in all cases.Direct closure of the VSD was undertaken in 16 cases and other cases repaired with patches.Aortic valvuloplasty in 92 cases.and 5 patients underwent aortic valve replacement.The other 18 cases were directly repaired the VSD with patches.Results The results of surgical treatment is satisfactory.In the 4 months to 2 years follow up,10 patients died,NYHA cardic function 72 cases is Ⅰ,31 is Ⅱ and 2 is Ⅲ.Conclusion Early and concomitant surgical treatment ventricular septal defect associated with aortic valve insufficiency can obtain an ideal results.

Objective To analyze effects of thoracoscopy in the diagnosis and treatment of suspected diaphragmatic injury after thoracoabdominal stab wound.Methods Sixty-eight patients who received thoracoscopic diagnosis and management of diaphragmatic injuries due to thoracoabdominal stab wounds from April 2000 to October 2011 were retrospectively analyzed.Results Occult diaphragmatic injuries were found in 11 patients.Seven patients underwent thoracoscopic suture,of which five had synchronous laparotomy for inspected abdominal organ injuries.Pulmonary parenchymal lacerations occurred in 15 patients who received thoracoscopic repair or resection.Coagulated hemothorax in 13 patients were removed.Postoperative complications included pleural effusion in one patient,pneumonia in two and pulmonary atelectasis in one.Hospital stay was(7.9±13.5)days,without ICU stay.The length of drainage,operation time and intraoperative blood loss were(3.3±1.5)days,(45.6±78.1)minutes and(57.8±24.3)ml respectively.There was no conversion to thoracotomy.Thoracic CT scan was performed six months postoperatively,without hernias.The accuracy of thoracoscopy in diagnosing diaphragmatic injury was 100％.Conclusion Thoracoscopy should be performed for the thoracoabdominal stab wounds with stable hemodynamics,with definite significance especially for the diagnosis and treatment of wounds at the 7-9th intercostal spaces.

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.

BACKGROUND:Recently,the development of tissue-engineered technique lms broadened the study of artificial esophagus.Some investigators have inoculated esophageal epithelial cells cultured in vitro onto compound polymer material and successfully constructed tissue-engineered esophagus.OBJECTIVE:To investigate the feasibility of tissue-engineered artificial esophagus by combining dog esophageal epithelail cells and an acelhilarized porcine thoracic aorta allogenic matrix.DESIGN:An experimental observation.SETTING:Central Laboratory,Taishan Medical College.MATERIALS:This study was carried out in the Central Laboratory.Talshan Medical College from June to December in 2004.Three hybrid dogs,24-hour-old,were provided by the Laboratory Animal Center,Taishan Medical College.The protocol was performed in accordance with ethical guidelines for the use and care of animals.The experimenhal instruments and reagents were as follows:CO2 incubator(MCO-15AC,SANYO),hypothermal high-speed centrifuge(RC-26,Dupont),trypsin,transferrin,type Ⅱ collagenase(Gibco),dulbecco's modified eagle's medium(DMEM),DispaseⅡ isolated enzyme,and rat monoclonal anti-keratin antibody(Sigma).METHODS:Acellularization of porcine aortas was performed by a method of enzyme-detergent.Esophageal epithelial cells of hybrid dogs were in vitro isolated,cultured and proliferated.Next,they were inoculated onto an acellularized porcine thoracic aortas allogenic matrix seaffold.Three and seven days later,the growth of esophageal epithelial cells on the acellularized matrix was observed under an electron microscope.MAIN OUTCOME MEASURES:Morphology of esophageal epithelial cells cultured in vitro;Biocompatibility of acellular matrix and dog esophageal epithelial cells.RESULTS:The acellularized procedure resulted in an almost complere removal of the cells and the loose three-dimensional matrix.The acellular matrix could be reseeded with expended esophageal epithelial cells in vitro.and esophageal epithelial cells had the potential of spread and proliferation.CONCLUSION:Acellular matrix possesses satisfactory biocompatibility for allogenic esophageal epithelial cells.Tissue-engineered artificial esophagus can be generated in vitro by a combination of esophageal epithelial cells and allogenic aceilularized matrix.

Objective:To analyze the learning effect of laparoscopic radical cystectomy(LRC)+ modified ileal conduit(MIC).Methods:From 2014 to 2019, 42 patients underwent MIC and their clinical data was retrospectively analyzed. 34 operations were performed by surgeon 1 and 8 operations by surgeon 2. We divided the 34 patients of surgeon 1 into three groups according to their surgical sequence (group A, 1st to 12th; group B, 13th to 23th; group C, 24 th to 34 th), the 8 cases of surgeon 2 was regarded as group D. The history of abdomen surgery in the 4 groups were 0, 1, 4, 3 cases, respectively ( P<0.05). There was no significant difference of the other baseline characteristics, such as age, BMI, American Society of Anesthesiologists. Then we compared several variables between the 4 groups like operation time, time of ileal conduit construction, blood loss, complication rate, lymph node yield, surgical margin, etc. The key steps of the MIC included isolating terminal ileum when the mesentery was transilluminated, performing end-to-end reflux ureterointestinal anastomosis after the efferent loop was fixed, closing the rent of the retroperitoneum. Results:All operations were performed intracorporeally with no transition to open surgery. The operative time for group A, B, C were 330.0(320.0, 360.0)min, 300.0(250.0, 308.0)min, 270.0(216.0, 324.0)min, respectively ( P =0.010). The time of ileal conduit construction of the 3 groups were 136.5(131.3, 147.5)min, 92.0(79.0, 119.0)min, 79.0(72.0, 115.0)min, respectively ( P <0.001). In addition, the difference of the two variables above between A and B, A and C groups separately reached statistical significance ( P<0.05), while the difference between B and C groups did not ( P>0.05). Other variables, such as blood loss, complication rate, lymph node yield, surgical margin, between the 3 groups reached no statistical significance ( P>0.05). The operative time of group D was 420.0(350.0, 450.0)min, and it reached statistical significance ( P<0.05) when compared with group A. There were no significant differences in other variables, such as blood loss, complication rate, lymph node yield, surgical margin, among the 2 groups ( P>0.05). Conclusions:The learning effect of LRC+ MIC was obvious. When surgeon volume increased, the operative time decreased significantly. Variables like estimated blood loss and complication rate of the 2 surgeons did not reached significant difference, which indicated reproductivity and safety of this procedure.

Spinal cord injury is very high morbidity trauma, seriously affecting the survival and health of patients. To establish a standard animal model has a great significance for studying SCI pathogenesis and pathological changes. A spinal cord injury device for experimental animal was presented in this paper. It can implement fixed-point and fixed-quantity impact by new design. It also can create many animal models of different levels injury. More importantly, it has many advantages such as simple to operate, free from human disturbance, high accuracy and reproducibility. Finally, some existing constraints and challenges about the animal spinal cord injury models made by the device were discussed.

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.

A 35-year-old female patient with a history of significant epidemiological exposure firstly visited eye doctor due to acute tarsadenitis in the right eye.Subsequently, she developed subconjunctival hemorrhage, fever and cough and received topical administration of antibiotics and systemic treatment of antiviral drug.Shortly thereafter, both his mother and father, who denied COVID-19 associated epidemiological history, appeared fever, fatigue and other symptoms and diagnosed as COVID-19.This female patient was diagnosed as COVID-19 by CT image of lung and COVID-19 RNA detection 17 days and 24 days after firstly visited eye doctor, respectively, and received specialized isolation treatment.The symptoms of COVID-19 are very varied, eye doctors should keep alert and pay attention to personal protection.