Hypoxia-inducibIe factor-1(HIF-1)is a main nucIear transcription factor for response to intratumor hypoxia. RecentIy,it has become a hot spot to attempt to improve hypoxia by inhibiting HIF-1. HIF-1 inhibitors' mechanisms of action are wide,which infIuences the two signaI transduction pathways that are phosphatidyIinositoI-3-kinase/ protein kinase B/ mammaIian target of rapamycin and Ras/ Raf/ mitogen-activated protein kinase kinase1-2/ extraceIIuIar signaI-reguIated kinase1-2,inhibits the function of heat shock protein 90,and reduces transcriptionaI activity of HIF-1. In combination with radiation,HIF-1 inhibi-tors significantIy enhance radiosensitivity and weaken radioresistance of hypoxia ceIIs,which contributes to the therapeutic effect of tumor irradiation.

Background and purpose: Epithelial ovarian carcinoma is the most malignant tumor in female reproductive system because of its resistance to chemotherapy. Fructose-1, 6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis used to catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate and inorganic phosphate, thereby inhibiting the effect of glycolysis in tumor cells. This study aimed to investigate the association between the expression of FBP1 and chemosensitivity. Methods: The expression level of FBP1 in ovarian cancer patients was measured by immunohistochemistry. Results: According to the results of immunohistochemistry in 209 ovarian carcinoma specimens, the percentage of positive FBP1 expression was about 49.3% (103/209). Loss of FBP1 was a negative factor of survival (42.6 months vs 62.1 months, P=0.003). Besides, patients who were sensitive to chemotherapy displayed significantly higher scores of FBP1 expression than patients who were resistant to therapy (P=0.007). Conclusion: The rate-limiting enzyme FBP1 in gluconeogenesis can be used as a biomarker for predicting the chemoresistance and prognosis of ovarian cancer patients.

Objective To detect content of 4-hydroxy-3-methoxy benzoic acid by RP-HPLC and observe the inhibitory effect of phloroglucinol on catecholamine-O-methyl transferase (COMT). Methods This study used the principle of 3,4-dihydroxy benzoic acid transforming to 4-hydroxy-3-methoxy benzoic acid under COMT’ s catalytic action. COMT (20 μL) was extracted from mouse liver homogenate. In a reaction system,10 μL catecol (1í10-3 mol·L-1 ) and 10 μL phloroglucinol (5í10-3 , 1í10-3 and 2í10-4 mol·L-1 ,respectively) were added. Products were determined by RP-HPLC to analyze effects of 4-hydroxy-3-methoxy benzoic acid on COMT. Results Phloroglucinol had inhibitory effect on COMT activity at concentrations of 5í10-3 mol·L-1 ,1í10-3 mol·L-1 and 2 í10-4 mol ·L-1 ,with the inhibition rate being 25. 3% ,17. 6% and 8. 9% ,respectively. Conclusion Phloroglucinol has an inhibitory effect on COMT activity,which is weaker than the effect of catechol of the same concentration.

Background The suppression of retinal angiogenesis is one of primary treatment targets for retinal vascular diseases,so seeking the intervention targets of retinal neovascularization is a hot research.Studies showed that insulin-like growth factor 1 (IGF-1) can promote the growth and restrain the apoptosis of vascular endothelial cells.However,whether IGF-1 is an intervention target for the treatment of retinal vascular diseases is unelucidated.Objective This study was to address the effects of IGF-1 on the migration,apoptosis and capillary tube formation of human retinal vascular endothelial cells (HRECs) and mechanism.Methods HRECs were cultured in vitro,and the cells in the exponential phase were prepared for subsequent experiments.The expression of IGF-1R mRNA in the cells was examined using reverse transcriptase PCR assay.Different concentrations of IGF-1 were added in the medium based on the difference of tests.The relative free-cell area difference (△S) after test was measured by Photoshop CS4 software and compared among 0,10 and 200 ng/ml IGF-1 groups 12 and 24 hours after cell scratching,respectively.The cell apoptotic rate was assayed by flow cytometry and compared between 0 ng/ml IGF-1 group and 1 000 ng/ml IGF-1 group,and the number of capillary tubes was examined by Matrigel test and assessed among 0,10,100 and 200 ng/ml IGF-1 groups 24 hours after addition of IGF-1.The expressions of platelet derived growth factor (PDGF)-BB mRNA and caspase-3 mRNA in the cells of the 0,500 and 1 000 ng/ml IGF-1 groups were detected by real-time fluorescence quantitative PCR after adding IGF-1 for 6 hours.Results Cultured cells grew well and attached 90％ confluence 2-3 days after incubation,and IGF-1R mRNA was positively expressed in the cells.In 12 and 24 hours after scratching,the relative migrating area of the cells was gradually reduced with the increase of IGF-1 contents.The △S was (4.83 ± 0.61) × 105 μm2 in the 200 ng/ml IGF-1 group,which was significantly larger than (3.28±0.64) ×105 μm2 in the 0 ng/ml IGF-1 group 24 hours after stretching (t=-3.707,P=0.021).The apoptotic rate in the 0 ng/ml IGF-1 group and 1 000 ng/ml IGF-1 group was (18.77±2.37) ％ and (12.05 ±0.88) ％,with a significant difference between them (t =2.869,P =0.046).The number of intact tubes was significantly increased in the 200 ng/ml IGF-1 group compared with the 0 ng/ml IGF-1 group ([20.33±2.83]/well vs.[17.94± 1.96]/well;t =-2.940,P =0.042).Compared with 0 ng/ml IGF-1 group,the relative expression level of PDGF-BB mRNA was elevated and that caspase-3 mRNA was evidently reduced in the 1 000 ng/ml IGF-1 group (t=-3.489,P =0.025;t =7.287,P =0.002).Conclusions IGF-1 can promote the migration and angiogenesis of HRECs and inhibit the apoptosis of HRECs.These effects of IGF-1 probably are associated with the up-regulation of PDGF-BB and down-regulation of caspase-3 in the cells.

Objective:To study the diagnostic value of non-enhanced lesions on enhanced CT in lung consolidation for necrotizing pneumonia in children.Methods:A total of 101 cases of necrotizing pneumonia with air sacs on CT scan who were hospitalized in the Department of Respiratory Intervention, Qilu Children′s Hospital of Shandong University from August 2016 to September 2018 were enrolled in this study(group with air lucency). Besides, another 75 cases of lobar pneumonia with non-enhanced lesions in lung consolidation but without air sacs on enhanced CT were also included from the same hospital over the same period(group without air lucency). Clinical data of these patients were retrospectively collected and statistically analyzed.Results:The white blood cell count was (12.5±5.5)×10 9/L in group with air sacs and (10.8±4.1)×10 9/L in group without air sacs, and the difference was statistically significant( t=-2.161, P=0.032). There was no statistical difference between the group with and without air sacs in age, gender distribution, the course prior to admission, duration of fever after admission, length of hospital stay, medical expense, the neutrophils percentage in peripheral blood, C-reactive protein, the erythrocyte sedimentation rate, serum procalcitonin, serum D-Dimer, serum lactate dehydrogenase, serum albumin, bronchoscopy times, the bronchial mucosal erosion ratio, the mucus plug score, the lavage purulent lavage ratio, and the ratio of luminal stricture or atresia in late bronchoscopy(all P>0.05). Conclusions:The clinical course of patients with non-enhanced lesions in lung consolidation but without air sacs is almost identical to that of patients with air sacs on CT scan.The presence of non-enhanced lesions in lung consolidation can be used as diagnostic basis of necrotizing pneumonia in children.

Abstract: Objective To observe the curative effect of thread-hanging combined with cotton plug on stage Ⅲ paronychia. Methods Sixty-one patients with stage Ⅲ paronychia were selected and randomly divided into a treatment group and a control group. The treatment group (n=31) was treated with thread-hanging and tampon under local infiltration anesthesia, and changed dressing and tampon every day after operation. After the wound healed, the patient soaked his feet in warm water every day and changed the tampon himself until the symptoms subsided, and the knot did not receive special treatment, and the nail plate would naturally shed as it outgrew the paronychia. The control group (n=30) was treated with thread-hanging and nail groove reconstruction under nerve block anesthesia, and the dressing was changed every day after operation. After thread removal, the patients soaked their feet in warm water every day until the symptoms subsided, and the knot was not specially treated, and it naturally fell off with the growth of the deck beyond the nail groove. The postoperative Visual Analog Scale (VAS) pain score, pain duration, wound healing time, cure rate, effective rate and recurrence rate of paronychia, and patients' satisfaction with the operation were compared between the two groups. Results Compared with the control group, the treatment group had lower VAS pain scores on the first and third postoperative days (2.1±0.3) and (0.2±0.1) vs. (6.3±0.1) and (3.2±0.2), respectively, shorter duration of pain and wound healing time (3.3±0.3) days and (10.1±0.5) days vs. (5.2±0.3) days and (15.2±0.3) days, respectively, higher cure rate (87.1% vs. 66.7%), lower failure rate (12.9% vs. 33.3%), lower recurrence rate (7.4% vs. 20.0%), and higher patient satisfaction (97.0% vs.75.3%). The treatment group showed significant superiority over the control group in all outcomes. Conclusion For patients with stage Ⅲ paronychia, thread-hanging combined with cotton tampon without nail groove reconstruction is advantageous as it avoids additional skin trauma, and does not affect the nail appearance and normal periungual barrier after healing, , reduces patient discomfort, and shortens the time off work, resulting in a higher cure rate. This treatment approach is therefore worth promoting in clinical practice.

Objective To investigate the efficiency of intraclot microbubbles (MB) combined with urokinase (UK) mediated ultrasound (US) thrombolysis.Metho ds Fifty clots prepared by bovine whole blood were equally divided into 5 groups and were treated in a circulation system with collateral circulation tube.The clots were treated by US,MB and UK in group 1,by US and MBingroup 2,by US and UK in group 3 and by UK in group 4.The group5 was the control group without any treatment.The thrombolysis rate of each group was measured and compared.Residual clots were histologically observed with hematoxylin-eosin staining and immunofluorescence.Results The thrombolysis rate of group 1 ([73.64±14.16]％) was significantly higher than group 2 ([47.97± 11.66]％),group 3 ([57.33±8.65]％),group 4 ([50.85±9.63]％),and group 5 ([29.76±18.06] ％,all P＜0.05).Histological examination of the clots in group 1 showed multiple thrombolysis foci with clots collapse,and the degradation of fibrin network was further confirmed by immunofluorescence.Conclusion The intraclot MB mediated US thrombolysis combined with UK can enhance the rate of thrombolysis in vitro experiment.

Background and purpose:Cervical cancer remains the second leading cause of death in gynecologic malignancies partially because of resistance to chemotherapy. Bufalin, a component of the traditional Chinese medicine Chansu, has been widely used in cancer treatment in China. This study aimed to investigate the effects of bufalin on inhibiting the proliferation of ME180 and C33A and explore its possible mechanism.Methods:The cytostatic effects of bufalin on ME180 and C33A cells were evaluated by CCK8 assay (cell counting kit-8). Glucose levels in ME180 and C33A cells were measured using glucose assay kit. Then the alterations of GLUT1 (glucose transporter 1) and HK2 (hexokinase 2) gene expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of proto-oncogene C-MYC and HIF1α (hypoxia-inducible factor 1α) were determined by Western blot.Results:According to the results of CCK-8, bufalin can significantly inhibit the proliferation of carcinoma cells ME180 and C33A (P=0.027,P=0.018). Test on glycometabolism indicated that glucose uptake in cells treated with bufalin decreased (P=0.034,P=0.036). Results from real-time PCR showed that the expression of glycometabolism related indicators GLUT1 (P=0.019) and HK2 (P=0.016) levels were signiifcantly down-regulated in bufalin treated group. Western blot showed that the expression of C-MYC and HIF1αin cells with bufalin treatment was down-regulated markedly.Conclusion:Bufalin can inhibit the proliferation of the cervical carcinoma cells ME180 and C33A through inhibition of their glucose metabolism.

Objective To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma(OCCC)tissues and its clinical significance.Methods A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery(SCS),who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1) protein expression in paraffin-embedded tissues. Results The positive rates of EGFR, HER2, AURKA, BRCA1,BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20%(8/40)vs 30%(7/23),22%(9/40)vs 35%(8/23),38%(15/40)vs 35%(8/23),42%(17/40)vs 39%(9/23),20%(8/40)vs 22%(5/23), 25%(10/40)vs 17%(4/23), and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ2-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC(4 months vs 10 months,log-rank test,P<0.05 for HER2;and 4 months vs 10 months,P<0.05 for AURKA);and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2;and 13 months vs 43 months, P<0.05 for AURKA). However,multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

OBJECTIVE: To study the effects and mechanism of couplet medicines of Scutellaria baicalensis-Paeonia lactiflora on improving ulcerative colitis (UC) in mice. METHODS: A total of 70 mice were randomly divided into blank group, model group, S. baicalensis group (1. 5 g/kg), P. lactiflora group (1. 5 g/kg), S. baicalensis-P. lactiflora (2:1, 1:1, 1:2, m/m) groups (total amount of 1. 5 g/kg), with 10 mice in each group. Except for blank group, UC model of mice was induced in each group. The next day after modeling, treatment groups were given relevant medicine liquid 0. 2 mL/10 g (75 mg/mL, calculated by crude drug mass concentration), while blank group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 7 d. After administration, disease activity indexes (DAI) of rats were scored, and the serum levels of TNF-α, IL-1β, IL-6, D-LA and myeloperoxidase (DAO) were determined. The length of the colon was measured and the intestinal mass index was calculated in mice. The activities of medullary peroxide (MPO) and SOD, the levels of NO and MDA were determined in colon tissue. RESULTS: Compared with blank group, DAI score, serum levels of TNF-α, IL-1β, IL-6, D-LA and DAO, the levels of MPO, NO and MDA in colon were increased significantly in model group, while the length of colon, intestinal mass index and SOD level of colon tissue were decreased significantly, with statistical significance (P<0. 05 or P<0. 01). Compared with model group, DAI score, serum levels of TNF-α, IL-1β and DAO, the level of MDA in colon were decreased significantly in S. baicalensis group (P<0. 05 or P<0. 01). The serum levels of TNF-α and IL-1β, the level of MDA in colon were decreased significantly in P. lactiflora group (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (2:1) group were improved significantly except for the length of colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:1) group were improved significantly except for serum level of IL-6 and the level of SOD in colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:2) group were improved significantly except for serum level of NO (P<0. 05 or P<0. 01). CONCLUSIONS: The couplet medicines of S. baicalensis-P. lactiflora can reduce the expression of proinflammatory factors, enhancing antioxidant activity of the body and decrease intestinal mucosal permeability so as to improve UC symptom of mice; and the effect of S. baicalensis-P. lactiflora (2:1) group is the best.