Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma (HCC).It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy.The molecular events underlying the process of VM formation are still poorly understood.In this study,we attempted to elucidate the relationship between Notch4 and VM formation in HCC.An effective siRNA lentiviral vector targeting Notch4 was constructed and transfected into Be17402,a HCC cell line.VM networks were observed with a microscope in a 3 dimensional cell culture system.Cell migration and invasion were evaluated using wound healing and transwell assays.Matrix metalloproteinases (MMPs) activity was detected by gelatin zymography.Furthermore,the role of Notch4 inhibition in Be17402 cells in vivo was examined in subcutaneous xenograft tumor model of mice.The results showed that downregulation of Notch4 destroyed VM network formation and inhibited migration and invasion of tumor cells in vitro (P＜0.05).In vivo,tumor growth was also inhibited in subcutaneous xenograft model (P＜0.05).The potential mechanisms might be related with down-regulation of MT1-MMP,MMP-2,MMP-9 expression and inhibition of the activation of MMP2 and MMP9.These results indicated that Notch4 may play an important role in VM formation and tumor invasion in HCC.Related molecular pathways may be used as novel therapeutic targets for HCC antiangiogenesis therapy.

Wound combined with total body irradiation (TBI) injury results in impairment of tissue repair and delayed processes of healing, so it has been considered as an important and representative model of impaired wound healing, but the mechanism is not fully clarified. Fibroblasts in wound are the most important cells participating in tissue repair, whereas its radiosensitivity is not high. To understand whether TBI injury has direct damaging effects on fibroblasts in wound, fibroblasts in wound combined with TBI injury and in wound of simple incision injury were isolated and cultured, and parameters associated with tissue repair were determined. The results showed that the abilities of proliferation, attachment and adhesion of fibroblasts isolated from wounds combined with TBI injury significantly decreased as compared with those of simple incision injury, nevertheless, apoptotic ratio of fibroblasts isolated from wounds combined with TBI injury increased significantly. These data suggest that TBI injury may cause direct damaging effects on fibroblasts in wounds, which might be one of the dominant reasons for impairment of wound healing when it is combined with TBI injury.
Animals ; Disease Models, Animal ; Fibroblasts ; metabolism ; physiology ; radiation effects ; Radiation Injuries, Experimental ; metabolism ; Rats ; Rats, Wistar ; Skin ; injuries ; Whole-Body Irradiation ; Wound Healing ; physiology

Combined radiation-burn injuries mainly occur under the circumstances of nuclear explosion, nuclear accident, nuclear terrorism, depleted uranium attack, as well as secondary injuries following attack on nuclear installation. Combination of burn and radiation injuries bring along more serious whole body damage, more complicated pathological mechanism and much more difficult management. Research progress on the pathological mechanism and medical management of several key links of combined injury were discussed in this paper. (1) Enhancement of early first aid and prevention of early death of wounded. (2) Damage and restoration of hemopoietic function. (3) Disturbance of immune function and prevention and treatment of infection (mainly on the intestinal mucosa immunity and enterological infection). (4) Management of burn wound. (5) The role of several important measures in the comprehensive treatment.
Animals ; Burns ; therapy ; Combined Modality Therapy ; Dogs ; Humans ; Multiple Trauma ; therapy ; Radiation Injuries ; therapy ; Rats

Objective To study the pharmacokinetic characteristics of meptazinol after single oral dose and multiple doses of meptazinol hydro-chloride capsule in Chinese healthy volunteers.Methods A random-ized, open, 3 ×3 Latin square design was adopted.Twelve healthy vol-unteers were divided into six groups , two people ( one male and one fe-male) per group.The dosages are 100 mg, 200 mg and 400 mg in single dosage study , and 200 mg every 6 hours for 5 times in multiple dosage study.The concentrations of meptazinol in plasma were determined by HPLC -MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 6.1 software.Results The main pharmacokinetics parame-ters of meptazinol in three single dose were as follow: Cmax were (22.21 ±12.74), (55.01 ±36.38) and (97.80 ±64.23) μg· L-1;tmax were (1.00 ±0.54),(1.04 ±0.61) and (1.54 ±0.91) h; t1/2 were (2.31 ±0.24), (2.31 ±0.24 ) and (2.46 ±0.59 ) h; AUCinf were ( 50.78 ±13.14 ) , ( 134.06 ±56.90 ) and ( 281.34 ±135.34 )μg· h· L-1.The main pharmacokinetic parameters of meptazinol under multiple dose were as follow:Cssmin was ( 6.01 ±2.03 ) μg · L-1 , Cmax was ( 54.30 ±27.10 ) μg · L-1 , Cavg was (20.13 ±6.82) μg· L-1, tmax was(1.06 ±0.51) h, t1/2 was (2.62 ±0.24) h, and AUCinf was (149.63 ±50.49)μg · h· L-1.Conclusion The plasma concentrations of meptazinolin in Chinese healthy volunteers were proceeded in an apparently mono-exponential fashion after a single oral dose from 100 mg to 400 mg meptazinol hydrochloride cap-sula.Meptazinol has no accumulation in the human body , after multiple doses of 200 mg every 6 hours for 5 times.The accumulation of meptazinol is consistent with linear pharmacokinetic process.

Objective To evaluate the effect of endoscopic surgery using the low-temperature plasma radiofrequency for nasal hemangioma.Methods Clinical data of 15 patients treated between October 2007 and Ocwber 2009 under endoscopic surgery using the low-temperature plasma radiofrequency were retrospectively studied.Results All tumors in 15 patients were completely removed.The blood loss was 1-150 ml and the average blood loss was about 15 ml,only gelatin sponge was used to protect the wound after operation.There was no additional packing to stop bleeding.No complications were seen.The patients had mild postoperative pain.All patients were followed-up from 2 months to 2 years,no recurrence was found.Conclusions Endoscopic surgery using low-temperature plasma radiofrequency for nasal hemangioma has following advantages such as simplicity,minimal invasion and so on.It is a viable surgical method for the treatment of nasal hemangioma.

AIMInducing mesenchymal stem cells (MSCs) differentiate to myoblasts with 5-azacytidine(5-Aza-CR), investigating the expression of Myf5 and the role of the signal transduction case of p38 in all the course of differentiation.

METHODSSeparating and purifying bone marrow-derived MSCs, inducing MSCs differentiation to myoblasts with 10 micromol/L 5-Aza-CR, assaying the gene expression time of Myf5 with RT-PCR method, the antigen expression of myosin with immunohistochemistry method and observing the changes of the activity of phosphorylation p38 before and after inhibited by SB203580 with Western-blot method.

RESULTSMSCs begin to express Myf5 delayed to the 9th day after inhibited by SB203580. Some of MSCs express myosin at the 7th day after induced; The phosphorylation p38 activity of MSCs enhanced after induced by 5-Aza-CR but obviously decreased after inhibited by SB203580.

CONCLUSIONMSCs can express myogenic regulator factors and orientation differentiate to myoblasts after induced by 5-Aza-CR, p38 really have a positive signal transduction affection in this course.

Animals ; Azacitidine ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred BALB C ; Myoblasts ; cytology ; Myogenic Regulatory Factor 5 ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the relationship of (TAAAA)n repeat polymorphism in the promoter of the sex hormone-binding globulin (SHBG) gene and SHBG serum levels to the glucose metabolic status of Chinese polycystic ovary syndrome (PCOS) patients in Shandong province.

METHODSGeneScan method was used to detect and identify (TAAAA)n repeat number (alleles) and genotypes for 156 controls and 157 patients who were divided into normal glucose tolerance without hyperinsulinemia (NIR group) and with hyperinsulinemia (HI group) and abnormal glucose metabolic (AGM) group according to the results of oral glucose test and insulin resistant test; IRMA was used to measure serum SHBG for part of them.

RESULTSFive alleles containing (TAAAA) 6-10 repeats and 14 genotypes including 6/6, 6/7, 6/8, 6/9, 6/10, 7/7, 7/8, 7/9, 7/10, 8/8, 8/9, 8/10, 9/9, 9/10 repeats genotypes were present in the subjects. Genotype distribution of 6/10 repeats genotype is lower in PCOS than that in control, and 8/9 repeats genotype vice versa (P < 0.01); among PCOS subgroups, the eight repeat genotypes in NIR group is more frequent than that in HI group (P < 0.01), and 7/9 genotype distribution in AGM group is higher than that in NIR group and HI group(P < 0.05-0.01). The serum SHBG levels in homozygous genotype groups exhibit a sequence of 8/8 > 9/9 > 6/6, 7/7 repeats and the fall of serum SHBG trend is in reversed relation with the increase in body mass index (BMI), Homa-IR, and blood pressure. Serum SHBG levels in AGM exhibit a sequence of HI group < NIR group < control but show no statistical difference between both groups.

CONCLUSIONThis study reveals that the repeat number, alleles, genotypes and their distributions in Chinese women are very different from these in foreigners. Some special genotypes and low serum SHBG levels may be associated with PCOS and its glucose metabolic status; some special genotypes may influence Chinese serum SHBG and need more studies, but both SHBG gene polymorphism genotype and serum SHBG are not good indicators to find out the PCOS individual at high risk.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blood Glucose ; metabolism ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Glucose ; metabolism ; Humans ; Polycystic Ovary Syndrome ; blood ; ethnology ; genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Repetitive Sequences, Nucleic Acid ; genetics ; Sex Hormone-Binding Globulin ; genetics ; metabolism

OBJECTIVETo investigate the expression of manganese superoxide dismutase (MnSOD) and to determine the relationship between MnSOD expression and clinicopathological features, biological behaviors in esophageal carcinoma.

METHODSImmunohistochemistry (SP) and RT-PCR were respectively used to detect the expression of MnSOD in 45 specimens of esophageal carcinoma tissues and normal esophageal mucosa (5 cm distant from the margin of cancer).

RESULTSThe positive rate of MnSOD protein expression was 31.1% in esophageal carcinoma tissues, significantly lower than 86.7% in the normal tissues (P < 0.05). The expressions of MnSOD mRNA and protein were significantly correlated with the lesion length, depths of invasion and histological grade (P < 0.05), but not with lymph node metastasis, lesion site and gross type of the tumor (P > 0.05). The relative content of MnSOD mRNA was (0.310 ± 0.036) and (0.482 ± 0.053) in the cancer and normal tissues, respectively, with a significant difference between the two groups (P < 0.05). The relative content of MnSOD mRNA was significantly related to lesion length, depths of invasion and histological grade (P < 0.05), but not correlated with lymph node status, lesion site and gross type of the tumor (P > 0.05).

CONCLUSIONThe expression of MnSOD protein and mRNA is decreased in esophageal carcinoma, suggesting that MnSOD gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of MnSOD expression may be useful in diagnosis, treatment and prognosis of esophageal carcinoma.

Adult ; Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Esophageal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase ; genetics ; metabolism

OBJECTIVETo explore the role of HOXB2 gene in the proliferation of primary human umbilical vein endothelial cells (HUVECs) and the protective effects of VEGF on the endothelia against radiation injury.

METHODSHUVECs were isolated, cultured, subcultured and identified. (1) Liposome coated oligodeoxynucleotide (odn) and homeoboxB2 antisense oligodeoxyncleotide (HOXB2asodn) were prepared prepared in the concentrations of 0.25, 0.5, 1.0 and 2.5 mg/L for the stimulation of HUVEC. (3)H-TdR incorporation test and MTT method were employed to determine the proliferation activity of HUVECs after activation. The cell cycle analysis of HUVECs was determined by flow cytometry. The expression level of HOXB2mRNA within HUVECs was detected by RT-PCR (reverse transcription polymerase chain reaction). (2) HUVECs were separately treated with the addition of VEGF in concentration of 50 microg/L, by radiation in the dose of 6 Gy or 12 Gy (60)Co gamma gamma ray, or radiation with 12 Gy (60)Co gamma gamma ray followed by the addition of VEGF in dose of 50 microg/L. The cellular morphology was observed and the cellular proliferation activity was determined by MTT method.

RESULTS(1) The proliferation activity of HUVECs could be markedly inhibited by liposome coated HOXB2asodn in comparison to liposome-odn (P < 0.05 or 0.001), and the inhibition effect was positively correlated with the increase in asodn concentration. The cell ratio in S phase and the expression level of the HOXB2mRNA could be lowered by asodn in dose of 2.5 mg/L (P < 0.05 or 0.001). (2) Radiation by (60)Co gamma ray could lead to the nuclear enlargement, vacuolation in the cytoplasm, multiplicity of nucleus and nuclear swelling. The proliferative activity of HUVECs was increased from 0.365 +/- 0.047 and 0.487 +/- 0.022 without radiation to 0.557 +/- 0.042 and 0.648 +/- 0.021 24 and 48 hours after 6 Gy radiation However it was decreased to 0.263 +/- 0.038 and 0.306 +/- 0.024 (P < 0.01) after 12 Gy (60)Co gamma ray radiation. Nevertheless, the cell morphology was obviously improved and the proliferation was enhanced by the addition of VEGF after 12 Gy radiation.

CONCLUSIONHOXB2 gene played important roles in the biological activities of HUVECs. Small dose (6 Gy) gamma-radiation could promote, but large dose (12 Gy) could decrease the mRNA expression of HOXB2 gene in HUVECs. In addition, VEGF could protect HUVECs against radiation injury.

Cell Proliferation ; drug effects ; radiation effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; radiation effects ; Endothelium, Vascular ; cytology ; drug effects ; radiation effects ; Genes, Homeobox ; genetics ; Homeodomain Proteins ; genetics ; Humans ; Liposomes ; pharmacology ; Oligonucleotides, Antisense ; genetics ; Radiation Injuries ; Transcription Factors ; genetics ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factors ; pharmacology

Objective　To compare the irradiation-protective and inter-synergestic effects of E838,WR-2721, Rubia cordifolia, cystamin e hydrochloride and ethinyl estradiol on radiation and combined radiation-burn injury. Methods　Above-mentioned drugs were given to the mice i ntraperitoneally, or intragastrcally, then, the mortality and the average surviv al d for 30 d were observed before and after the administration of the drug s. Results　①When drugs were before injury , the survival rate and the average survival d of the radiation and combined radiation-burn injured mice were increased obviously with the best effect in E838 and WR-2721. ②When drugs were given after injury, E838 and R. cordifolia also kept the effect. ③Combined appling WR-2721（pre) and E838（post）displayed a significant syner gistic reaction. Conclusion　E838 and WR-2721 are more e ffective than the others in the prevention of radiation.