1.Notch4 Inhibition Suppresses Invasion and Vasculogenic Mimicry Formation of Hepatocellular Carcinoma Cells
CHENG RUI ; CAI XIN-RAN ; KE KUN ; CHEN YAN-LING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2017;37(5):719-725
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.
2.Studies on the treatment of combined radiation-burn injury.
Chinese Journal of Burns 2008;24(5):387-389
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
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Burns
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therapy
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Combined Modality Therapy
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Dogs
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Humans
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Multiple Trauma
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therapy
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Radiation Injuries
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therapy
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Rats
3.Effects of total body irradiation injury on the participation of dermal fibroblasts in tissue repair.
Ji-Fu QU ; Tian-Min CHENG ; Lin-Shui XU ; Chun-Meng SHI ; Xin-Ze RAN
Acta Physiologica Sinica 2002;54(5):395-399
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
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Disease Models, Animal
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Fibroblasts
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metabolism
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physiology
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radiation effects
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Radiation Injuries, Experimental
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metabolism
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Rats
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Rats, Wistar
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Skin
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injuries
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Whole-Body Irradiation
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Wound Healing
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physiology
4.Pharmacokinetic study of meptazinol hydrochloride capsule in Chinese healthy volunteers
Chang-Cheng YANG ; Xin GUO ; Tao SU ; Zhi LIU ; Li-Ling RAN ; Ren GUO
The Chinese Journal of Clinical Pharmacology 2014;(8):685-688
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.
5.Endoscopic surgery using the low-temperature plasma radiofrequency for nasal hemangioma
Cui-Ping SHE ; Qing-Feng ZHANG ; Wei SONG ; Xin-Ran ZHANG ; Chen-Jing CHENG ; Tao PAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2010;45(3):197-199
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.
6.The role of p38 on the differentiation of MSCs to myoblasts.
Jin WANG ; Cheng-Ji LUO ; Xin-Ze RAN ; Hui XU ; Yong-Ping SU ; Tian-Min CHENG
Chinese Journal of Applied Physiology 2004;20(4):345-348
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
7.Experimental study on preventive and therapeutic effec ts of 5 radioprotectants on combined radiation-burn injured mice
Chao-Hua GUO ; Pei-Yan KONG ; Zhong-Min ZOU ; Yan-Hong ZHOU ; Jin-Ming ZHOU ; Yong ZHANG ; Cun-Meng SHI ; Xin-Ze RAN ; Cheng-Ji LUO
Journal of Third Military Medical University 2001;23(5):544-546
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.
8.Development and thinking of Chinese radiation medicine
Chinese Journal of Disease Control & Prevention 2019;23(11):1305-1308,1424
In this paper, we reviewed the initiation and development of radiation medicine in China, field researches on the health effects of nuclear test and the great leap from the final reports, advance in clinical diagnosis and treatment of radiation injury, and research of radiation combined injuries. Nowadays, China makes great efforts to move up further in development and peaceful use of nuclear energy as one nuclear power. So, nuclear development and nuclear safety have ushered in new opportunities and challenges. To this end, we must maintain a clear understanding, grasp new opportunities, meet new challenges, and be prepared for danger. Thus, a bright future for research in radiation medicine will come.
9.The role of diaphgram fatigue in the death from hanging with bound upper limbs of rabbits.
Fu-Xue JIANG ; Han-Lan JING ; Gui-Sheng OU ; Xin-Biao LIAO ; Yi-Jun ZHANG ; Yan-Geng YU ; Jian-Ding CHENG ; Zhao-Hui LI ; Xiao-Ran GUO
Journal of Forensic Medicine 2006;22(3):165-167
OBJECTIVE:
To explore the role of diaphgram fatigue in the death from hanging with bound upper limbs of rabbits.
METHODS:
Rabbits were hanged with upper limbs bound, then the data of EMGdi were gathered
RESULTS:
By analyzing power spectral of EMGdi in experiment, we compare the ratio change of H/L between pre-experiment and post-experiment. There is a significance decrease of the ratio of H/L, so it indicates that diaphgram fatigue does exist.
CONCLUSION
Diaphgram fatigue plays an important role in the death from hanging with limbs of rabbits bound.
Animals
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Asphyxia/physiopathology*
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Cause of Death
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Diaphragm/physiopathology*
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Electromyography
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Female
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Forensic Medicine
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Male
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Muscle Fatigue
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Rabbits
10.Effect of lipopolysacharide on the biological features and growth factor secretion power of U937 cell line.
Jia MING ; Xu-Sheng LIU ; Liang LIU ; Hui XU ; Xin-Ze RAN ; Tian-Min CHENG
Chinese Journal of Burns 2004;20(2):92-94
OBJECTIVETo investigate the effect of lipopolysacharide (LPS) in different concentrations on the biological features and growth factor secretion power of U937 cell line.
METHODSIn vitro cultured U937 cells were stimulated by 0 (as control), 0.1, 1.0, 10.0, 50.0 and 100 micro g/ml LPS respectively for 24 hours. Thereafter, the cell proliferation ability was determined by MTT method. The cell apoptosis rate was determined by flow cytometry. The changes in the contents of transforming growth factor beta(1) (TGFbeta(1)) and vascular endothelial growth factor (VEGF) of the supernatant of the cell culture were assessed by ELISA.
RESULTSApoptosis and TGFbeta(1) secretion could be induced by LPS in dose of 0.1 to 100 micro g/ml when compared with that without LPS challenge (P < 0.05 - 0.01). In detail, LPS in lower dose (0.1, 1.0 and 10.0 micro g/ml) could promote the proliferation of U937 (P < 0.05 - 0.01) but exerted no effect on VEGF secretion. In contrary, LPS in high dose (50 and 100 micro g/ml) could promote VEGF secretion (P < 0.01) but exerted no effects on the proliferation of U937 cells.
CONCLUSIONU937 cells could be activated to increase the secretion of TGFbeta(1) by LPS in optimal dose of 0.1 - 10.0 micro g/ml, but the secretion of VEGF could only be promoted by LPS in higher concentration.
Apoptosis ; drug effects ; Cell Division ; drug effects ; Humans ; Lipopolysaccharides ; pharmacology ; Transforming Growth Factor beta ; analysis ; secretion ; Transforming Growth Factor beta1 ; U937 Cells ; drug effects ; secretion ; Vascular Endothelial Growth Factor A ; analysis ; secretion