Hypoxia is very common in solid tumor.It results in a series of changes of biological behavior in tumor cells.Hypoxia could facilitate malignant cells metastasis,in which the hypoxia inducible factor-1 plays an important role.The hypothesis for the tumor cells to metastasis is the degradation of the extracellular matrix(ECM).The ECM can be degraded by the matrix metalloproteinase,which is a critical factor in the process of tumor-metastasis.So far,it is not clear whether hypoxia have a role in the regulation of MMPs in tumor.So this review summarize the advanced knowledge on the influence of HIF-1 and MMPs in tumor-metastasis and the interaction between two genes.

Background and purpose:HIF-1?、HER-2 and survivin are all considered as important prognostic factors of breast cancer,but the relationships among them are poorly understood.We investigated the expression of HIF-1?、HER-2 and survivin in Breast Carcinoma,and explored the relationship among the three prognostic factors.Methods:The expressions of HIF-1?、HER-2 and survivin were detected by immunohistochemistry in 51 human Breast Carcinoma samples.Results:① 28(54.88%),11(21.69%) and 35(68.62%) were positive for HIF-1?、HER-2 and survivin,respectively.② A significant difference was found in terms of the overexpression of HER-2 between the samples with HIF-1? either positive or negatiwe(P0.05).Conclusions:The positive expression of HIF-1? was strongly correlated with the overexpression of HER-2,but not survivin in breast carcinoma.

Background and purpose:Hypoxia induced the decreased radiosensitivity of tumor cells, which was the cause of tumor radioresistance and relapse and metastasis. During the course, HIF-1a played the most important role in the regulation of hypoxia. However, it’s still unknown about the effect of HIF-1a on the radiosensitivity of hypoxia tumor cells and the relationship with autophagy. This study was to inhibit HIF-1αexpression in hypoxic lung adenocarcinoma cell line A549 with RNA interference (RNAi), and explore its effect on hypoxic cell radiosensitivity and autophagy. Methods: Plasmids pHIF-1α-shRNA and Neg-shRNA (negative control) were constructed and transfected into hypoxic A549 cells, this positive clone was named A549/HIF-1α-shRNA. Clone formation array was applied to calculate the value of D0, SF2, SER. The expression of HIF-1α, LC3, c-parp was detected by Western blot. Results:The SF2 of hypoxic A549 cell was 0.62, which was higher than that of normoxic A549 cell, SER was 1.45. The level of LC3Ⅱincreased significantly and the level of c-parp decreased after the radiation of hypoxic A549 cell. The level of HIF-1a increased in hypoxic A549 cells. The expression of HIF-1αin hypoxic A549 cells was suppressed markedly after transfection of HIF-1α-shRNA;this clone was named A549/HIF-1α-shRNA. The SF2 and SER were significantly lower in A549/HIF-1α-shRNA cells, 0.45 and 0.72 respectively. Under the hypoxic condition and after the inhibition of HIF-1α, the expression of LC3Ⅱ decreased significantly and the expression of c-parp increased. Conclusion:We successfully established a cell model that HIF-1αexpression was suppressed almost completely by RNAi. The inhibition of HIF-1αby shRNA may raise the radiosensitivity and decrease the autophagy of hypoxic A549 cells in vitro.

Objective To investigate the design and manufacture of 3D printed compensator in electron radiation therapy for Merkel cell carcinoma,and to verify the feasibility of this technique in electron radiation therapy.Methods Computed tomography was used to collect images of a human head phantom.The delineation of target volume of Merkel cell carcinoma was simulated in the planning system and a radiotherapy plan was formulated after adding the compensator.The compensator was printed out by a 3D printer and fixed on the head phantom.A second CT scan was performed to make a new treatment plan.For the two plans,several planes parallel to the beam were selected to calculate gamma passing rates.The actual dose distribution was measured using disposable films.The gamma passing rate was compared between the film system and the planning system.The conformity index (CI) and the heterogeneity index (HI) of target volume were compared between the plans using the printed compensator and the conventional compensator of the same thickness.Comparison between the two plans was made by paired t test.Results Using the dose distribution of the plan with simulated compensator,the gamma passing rate was 94.7±2.3％ in the plan with 3D printed compensator.Using the dose distribution measured by the film,the gamma passing rate was 96.6％ in the plan with 3D printed compensator.Compared with the conventional compensator,the 3D printed compensator achieved a significantly elevated CI (0.85 vs.0.69,P=0.004) and a slightly improved HI (1.30 vs.1.26,P=0.001).Conclusions The conformal dose distribution provided by 3D printed compensator for tumors at different depths meets the clinical need.

Summary: To study the effects of hypoxia on the expression of P-gp and mutltidrug resistance protein in human lung adenocarcinoma A549 cell line, and to explore the probable mechanism of hypoxia in tumor cell of MDR. The expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein was immunohistochemically detected by culturing human lung adenocarcinoma A549 cell under hypoxia (2 % O2) for 24 h. After interaction with adriamycin or cisplatin under hypoxia (2 % O2) for 24 h, the cell survival rate was detected by MTT. Our results showed that the expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein under hypoxia were higher than the expression under normoxia, and correlations between the expression of HIF-1α and P-gp or multidrug resistance-associated protein was observed (P<0.05). The resistance of adriamycin of A549 cell was enhanced under hypoxia. It is concluded that the resistance of tumor chemotherapy is enhanced in hypoxia. The expression of HIF-1α is obviously correlated with the expression of P-gp and mutltidrug resistance protein.

Most patients with primary liver cancer in China are in the advanced stage at initial diagnosis and lose the opportunity for surgical treatment, and therefore, how to reduce advanced liver cancer to resectable liver cancer is a hot topic in clinical research in recent years. The key premise of successful conversion is to screen out the individuals who are suitable for conversion or may achieve successful conversion through comprehensive examination and necessary multidisciplinary consultation. This article introduces the conversion strategy and the antitumor strategy for liver cancer with lung metastasis, portal vein tumor thrombus, massive tumor dissemination, or multiple tumors, liver cancer with liver function decompensation, liver cancer with liver cancer dissemination and metastasis and an ECOG constitution score of ＞2, and liver cancer with a high HBV load, which has certain guiding significance in the downstaging conversion therapy for advanced liver cancer in clinical practice.

Objective: To explore the effect of drawing therapy on the behavior of children with attention deficit hyperactivity disorder (ADHD), and to provide a new perspective for the treatment of children with attention deficit hyperactivity disorder (ADHD). Methods: In June 2019, a random sample of three primary schools in 1-6 grade in Baishan who diagnosed with ADHD was recruited, the experimental group 10 ADHD children were given painting therapy intervention for 14 weeks, four times a week, 120 mins each time, the control group 10 ADHD children received no intervention. During the study period all the participants do not receive any other treatment. The ADHD Rating Scale Parent version,the Conners Parents Symptom Questionnaire(PSQ) and the Rey Complex Figure test was assessed before and after the intervention to evaluate the symptoms of ADHD children. Results: In terms of PSQ score test, there were significant differences between the scores of four dimension factors in the experimental group after therapeutic intervention and those before intervention and those after intervention in the control group(P<0.05). The follow-up test showed that the PSQ score in the experimental group remained good (P<0.05). There were two dimension factors that were not significantly different in the post-test and follow-up post-test and before intervention. In Rey complex memory graph test score test, it was found that the score of four dimensions after intervention in the experimental group was significantly different from that before intervention and after intervention in the control group (P<0.05). After 12 weeks, the score of follow-up test remained good (P<0.05). Conclusion Painting therapy has a significant effect on ADHD children’s behavioral management ability and working memory ability, and the effect can last for at least 12 weeks.

Aim To study whether Ophiopogonin D has an effect inhibitory on myocardial hypertrophy induced by AngiotensinⅡand its possible mechanism. Methods Rat myocardial cell line H9 c2 were cultured in vitro. The effect of Ophiopogonin D on cell vitality was tested by;H9 c2 cells were treated with AngⅡ 1μmol ·L-1 after 24h to induce the cardiac hypertrophy,then it was co-treated with different concentrations of Ophio-pogonin D were added for 24h. After above,the total protein content was detected by BCA method;Quantita-tive real-time PCR ( qRT-PCR ) technique was used to examine the expression of marker genes BNP and β-MHC mRNA ,which representing the function of hear-ing; Western blot was used method to detect the ex-pression of autophagy protein LC3 B and high-through-put screening technology was emptoyed to verify it. In addi-tion, the changes of mitochondrial membrane po-tential in H9c2 myocardial cell were also examined. Results The cell viability results showed that H9 c-2 cells exposed to different concentrations of AngⅡ had no significant effect on vitality compared with the con-trol group after 24 h,but high concentrations of Ophio-pogonin D ( 50 ~100μmol · L-1 ) could obviously in-hibit the cell activity. Ot-her experimental results showed that myocardial cells treated with AngⅡ for 24h could cause myocardial hypertrophy,which appar-ently displayed the growth level of specific hypertrophic gene mRNA expression and the marked increase of the total protein expression. As hypertrophy was activated by AngⅡ, cells autophagy would be significantly en-hanced at the same time, more-over, the mitochondrial membrane potential would be reduced. But the effects of Ophiopogonin D could significantly reverse those pathological changes. Conclusion All above experi-mental results indicate that Ophiopogonin D can in-hibitmyocardial hypertrophy induced by AngⅡand pos-sibly plays a critical role in cardiovascular protection.

The expression of DNA ploidy, the cell cycle and Ki67 antigen in nasopharyngeal carcinoma (NPC) were studied and their relationship with the clinical biological behaviors and prognosis of NPC was evaluated. Biopsied specimens of NPC were made into cell suspension. By using cytometric double labeling Ki67 and DNA method, the expression of DNA ploidy, the cell cycle and Ki67antigen were analyzed. The patients were followed-up for about 3 years and the relationship between the above-mentioned parameters and the clinical biological behavior and prognosis of NPC were evaluated. Of the 62 cases of NPC, the DNA aneuploid accounted for 29.03 %. The S phase cells accounted for 0 to 54 % in the cell cycle and the positive expression of Ki67 ranged from 0 to 52 %.There were 40 cases of LPI (64.5 % ) including 15 negative cases and 22 cases of HPI (35.5 % ) respectively. The DNA anueploid content was positively related to the S phase cells. The patients having a low expression of Ki67 or DNA aneuploid in tumor cells were not sensitive to chemotherapy, liable to metastasis to distant organs and had a poor prognosis, while Ki67 showed no correlation with DNA ploidy and the cell cycle. It was suggested that DNA ploidy and Ki67 could be used as an independent and objective marker to evaluate the radiosensitivity and prognosis of NPC.

BACKGROUNDTo explore the expression level and its clinical significance of hypoxia inducible factor 1α (HIF-1α) in non-small cell lung cancer.

METHODSThe expression of HIF-1α was detected in 68 human non-small cell lung cancer samples by immunohistochemistry.

RESULTSThirty-nine (57.35%) out of 68 human non-small cell lung cancer samples were positive for HIF-1α. The positive rate of HIF-1α in adenocarcinoma was 54.76% (23/42) and 61.54% (16/26) in squamous cell carcinoma ( P > 0.05) respectively. The positive rate of HIF-1α in moderate- to well-differentiated samples was 74.29%(26/35) and 39.39%(13/33) in low-differentiated samples respectively ( P < 0.05). The expression rate of HIF-1α in I-II stage ( 86.96%, 20/23) was significantly higher than that in III-IV stage (42.22%,19/45)( P < 0.05). The positive expression of HIF-1α was not related to sex and age of patients and lymph node status.

CONCLUSIONSHigh expression of HIF-1α exists in non-small cell lung cancer, and it may be related to cell differentiation and TNM stage of tumor. The results suggest that resistance to radiotherapy and chemotherapy induced by HIF-1α should be considered in the treatment of non-small cell lung cancer.