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Ionizing radiation can induce the death of lymphatic endothelial cells, leading to structural damage, dysfunction, and reduction of lymphatic vessels, which poses a negative impact on radiotherapy. However, it can also induce tumor cells and tumor-infiltrated immune cells to secrete various cytokines and promote tumor-associated lymphangiogenesis, which favors anti-tumor therapy and improve anti-tumor immunity. Studying the changes in lymphatic vessels after ionizing radiation may be a way to explore the synergistic anti-tumor effects of radiotherapy and immunotherapy. This review summarized the morphological changes in lymphatics after ionizing radiation, the molecular mechanisms for the effects of ionizing radiation on lymphatic vessels, and the clinical value of lymphatic changes after ionizing radiation, aiming to provide ideas for the study of the effects of ionizing radiation on lymphatic vessels.
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Background and Objectives@#Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. @*Methods@#and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. @*Conclusions@#We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.
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Objective To observe the clinical effect of Yanshu compound radix sophore injection combined with radiotherapy in treatment of patients with bone metastases from lung cancer. Methods A total of 116 patients with bone metastases from lung cancer admitted to the Department of Radiation Oncology of Gansu Provincial Cancer Hospital from January 2014 to December 2018 were selected. The 58 patients were treated by using three-dimensional conformal radiotherapy (3D-CRT), zoledronic acid and oxycodone sustained-release tablets (control group); the others 58 patients were treated radix sphore injection on basis of control group (integrated Chinese and western medicine). The two groups were treated continuously for 10 days as 1 course of treatment, taking a rest for one week in the middle, then they took the second course of treatment; after the end of 2 courses, the therapeutic effects were evaluated in the two groups. The pain grading, Karnofsky functional status (KPS) score and myelosuppression were observed before and after treatment in two groups, respectively. Results The proportions of patients with painless and mild pain after treatment in the integrated Chinese and western medicine group were significantly lower than those in control group [painless: 22.41% (13/58) vs. 39.66% (23/58), mild pain: 10.35% (6/58) vs. 46.55% (27/58)], while the proportions of patients with moderate pain and severe pain in the integrated Chinese and western medicine group were significantly higher than those of the control group [moderate pain: 53.45(31/58) vs. 12.07% (7/58), severe pain: 13.79% (8/58) vs 1.72% (1/58), both P < 0.05]. After treatment, the proportion of patients with improved KPS score in integrated Chinese and western medicine group was significantly higher than that in control group [55.17% (32/58) vs. 36.21% (21/58), P < 0.05], and the proportion of patients with stable and decreased KPS score were less than that of control group [stable KPS score:18.97%(11/58) vs. 27.59%(16/58), decreased KPS score:25.86% (15/58) vs. 36.21% (21/58)]. The proportions of patients with blood cell count (WBC), hemoglobin (Hb) and platelet count (PLT) showing no myelosuppression (at the zero degree) after treatment in integrated Chinese and western medicine group were obviously higher than those in control group [WBC: 77.59% (45/58) vs. 36.21% (21/58), Hb: 77.59% (45/58) vs. 70.69% (41/58), PLT: 58.62% (34/58) vs. 32.76% (19/58), all P < 0.05]. Conclusion Yanshu compound radix sphore injection combined with radiotherapy can reudce bone metastasis pain, reduce bone marrow suppression and improve quality of life in patients with advanced lung cancer and bone metastasis.
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Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.
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Objective To investigate the role of circular RNA (circRNA) in the occurrence of psoriasis.Methods Mesenchymal stem cells were isolated from skin lesions of 15 patients with psoriasis (psoriasis group) and skin tissues of 15 healthy human controls (control group) separately,and then subjected to cultivation.Flow cytometry and cell differentiation assay were performed to identify these mesenchymal stem cells.RNA sequencing was conducted to measure the expression of circRNA,and detailed bioinformatics analysis was performed.Then,7 differentially expressed circRNAs were selected,and a circRNA-microRNA interaction network was established.In this network,3 related microRNAs were selected and validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Statistical analysis was carried out by a two-sample t-test for comparison of qRT-PCR results between the psoriasis group and control group.Results As RNA sequencing showed,a total of 6 323 circRNAs were identified,and 3 227 out of these circRNAs were first reported in this study.Compared with the control group,129 circRNAs were differentially expressed in the psoriasis group,including 123 up-regulated circRNAs and 6 down-regulated circRNAs.The predicted circRNA-microRNA interaction network showed that several psoriasis-related microRNAs were associated with the 7 circRNAs,such as miR-17-5p,miR-30e-5p,miR-142-3p/5p,miR-369-3p,miR-184,miR-4490,miR-654-3p and miR-423-5p.qRT-PCR also confirmed that the 7 differentially expressed circRNAs were up-regulated in the psoriasis group.Compared with the control group,the expression of the 3 selected microRNAs significantly decreased in the psoriasis group (t =3.993,3.217,2.918,respectively,all P ＜ 0.05).Conclusion There is aberrant expression of circular RNAs in the mesenchymal stem cells from psoriatic skin lesions,which may take part in the occurrence of psoriasis.
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OBJECTIVE:To investigate the utilization of opioid analgesic drugs in a hospital,so as to provide reference for ra-tional drug use in clinic. METHODS:The utilization of opioid analgesic drugs in the hospital during 2014-2016 was analyzed and compared retrospectively in terms of consumption sum,DDDs,DDC,B/A,etc. RESULTS:Annual consumption sum of opioid an-algesic drugs in the hospital increased slightly in 2015,but decreased significantly in 2016. Fentany transdermal patches(8.4 mg), Oxycodone and acetaminophen tablets and Remifentanil hydrochloride for injection always took up the first 3 places in the list of DDDs. DDDs of Fentanyl citrate injection(0.1 mg)and Morphine sulfate sustained-release tablets increased year by year;while DDDs of Fentany transdermal patches(4.2 mg)and Fentany transdermal patches(8.4 mg)decreased year by year. DDC of all opi-oid analgesic drugs decreased in 2016,with the cancel of drug price addition at the end of 2016. B/A values of most drugs were close to 1.0;while B/A value of Oxycodone hydrochloride sustained-release tablets(40 mg)was much less than 1.0,and that of Fentany transdermal patches(8.4 mg)and Oxycodone and acetaminophen tablets were significantly more than 1.0 for consecutive 3 years. CONCLUSIONS: The variety and specifications of opioid analgesic drugs in the hospital is comprehensive during 2014-2016. The clinical utilization of opioid analgesic drugs is generally rational,but still needs to be supervised effectively and par-ticularly,so as to improve standard use of opioid andalgesic drugs.
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OBJECTIVE:To establish drug use evaluation(DUE)criteria for tigecycline,and to provide reference for rational use of tigecycline. METHODS:Based on tigecycline instructions,referring to related specifications and literatures,DUE criteria for tigecycline was established. And on a basis of it,referring to DUE criteria,in retrospective study,the utilization of tigecycline in 179 inpatients of some one hospital during Nov. 2012-Oct. 2016 was evaluated and analyzed in respects of management indexes, medication indication,medication duration,medication results,etc. RESULTS:The results for DUE of tigecycline in this hospital was that the proportion of patients with consultation records was 83.2%(aiming at 100%);microbial inspection rate was 90.5%(aiming at 80%);the coincidence rate of medication indication was 98.9%(aiming at 90%);the rates of solvent selection,ad-ministration route,drug interaction,incompatibility,drug use in special populations meeting the criteria were all 100%(aiming at 100%);the rate of prescribing authority was 20.1%(aiming at 100%);the rate of drug dosage and medication interval meeting the criteria were 7.3%(aiming at 100%);response rate was 54.7%(aiming at 80%). CONCLUSIONS:Established DUE criteria of tigecycline can standardize the clinical utilization of tigecycline.
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Objective To assess the efficacy and safety of the carbon ion radiotherapy for stage Ⅰ non-small cell lung cancer (NSCLC).Methods We searched multiple electronic bibliographic databases,including the Cochrane library,PubMed,EMBASE,China Journal Full-text Database,Chinese Biomedical Database,and the Wanfang Database to assemble the available studies of carbon ion radiotherapy for stage Ⅰ non-small cell lung cancer.MetaAnalyst Beta 3.13 and STATA 12.0 software were used to combine the extracted data.Results Ten studies (seven trials) were included.The overall survival rates of 1,3 and 5 years were 95.1％,68.5％ and 45.9％,respectively.The local control rates of 1,3 and 5 years were 90.2％,76.7％ and 81.2％,respectively.The cause specific survival rate of 1,3 and 5 years were 82.9％,58.5％ and 57.3％,respectively.The rate of primary recurrence and total recurrence were 45.8％ and 11％,respectively.The rates of total death and death from lung cancer were 52.4％ and 28.3％,respectively.There were differences observed between T1 stage and T2 stage in regards to five year overall survival rate,total recurrence,lung cancer death,and grade 1 and grade 2 skin toxicities.Conclusions Available data demonstrate that carbon ion radiotherapy,in general,is a safe and feasible treatment modality for stage Ⅰ NSCLC.Although current results are promising,more evidence is required before carbon ion radiotherapy can become the international standard treatment for lung cancer patients.
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Objective:To prepare the thermosensitive nasal gel of ephedrine hydrochloride and diphenhydramine hydrochloride and establish its quality control method. Methods:The amounts of P407, P188 and PEG 6000 were optimized by an orthogonal test with the gelling temperature as the index. An HPLC method was established to determine the contents of ephedrine hydrochloride and di-phenhydramine hydrochloride. Results:The optimum amount of P407, P188 and PEG 6 000 was 19%, 2% and 1%, respectively. The linear range of ephedrine hydrochloride was 1.600 0-2.400 0 mg·ml-1(r=0.999 6), and the average recovery was 99.76%with RSD of 1. 02%(n=9). The linear range of diphenhydramine hydrochloride was 0. 160 0-0. 240 0 mg·ml-1(r=0. 999 7), and the average recovery was 101. 27% with RSD of 1. 10%(n=9). Conclusion:The formula design and preparation technology of the gel are feasible. The HPLC method is suitable for the quality control of the preparation.
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Objective To evaluate the inhibitory effect of mesenchymal stem cells (MSCs) in lesions of patients with psoriasis on T lymphocyte proliferation.Methods Tissue specimens were obtained from the lesions of 15 patients with psoriasis vulgaris (7 at progressive stage and 8 at resting stage) and normal skin of 15 human controls from the Department of Urology and Plastic Surgery,Taiyuan City Centre Hospital.MSCs were isolated from these skin specimens,cultured,and identified using flow cytometry and in vitro differentiation assay.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the concentration of interleukin (IL)-6,IL-1 1,hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β1 in the culture supernatant of third-passage MSCs.Peripheral blood T cells were obtained from a healthy adult and cocultured with the third-passage MSCs for four days.Then,cells were counted and methyl thiazolyl tetrazolium (MTT) assay was conducted to evaluate the proliferation of T cells.One-way analysis of variance (ANOVA) and Student-Newman-Keuls (SNK) test were carried out to compare the proliferation of T lymphocytes,and two independent samples t test to compare the concentrations of cytokines.Results Inverted microscopy revealed that the patient-and control-derived MSCs shared similar morphological properties and multi-directional differentiation capacity,along with the expression of CD29,CD44,CD73,CD90 and CD105,but absence of CD34,CD45 and HLA-DR on cell surface.After coculture with MSCs from the patients and controls for four days,the count of T lymphocytes per milliliter was (1.67 ± 0.34) × 105 and (1.04 ± 0.29) × 105 respectively (P＜ 0.01),and the proliferative activity (expressed as absorbence at 492 nm)was 0.317 ± 0.021 and 0.275 ± 0.007 respectively (P ＜ 0.01).Compared with the control-derived MSCs,the patient-derived MSCs showed a significantly higher level of IL-1 1 ((181.37 ± 31.74) vs.(130.07 ± 29.20) ng/L,t =5.32,P ＜ 0.01),but a lower level of lL-6 ((61.67±17.53) vs.(76.74±18.96) ng/L,t=2.61,P＜0.05)and HGF ((319.24 ± 41.03) vs.(352.35 ± 51.47) ng/L,t =2.25,P＜ 0.05),as well as a similar level of TFG-β1,in the culture supernatant.Conclusions The inhibitory effect of MSCs in psoriatic lesions on T lymphocyte proliferation is diminished,which may contribute to the pathogenesis of psoriasis.
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[Objective] To assess the changes in bone marrow microenvironment in patients with psoriasis by determining the level of transforming growth factor β1 (TGF-β1),stem cell factor (SCF),keratinocyte growth factor (KGF) and tumor necrosis factor-α (TNF-α) secreted by bone marrow stromal cells(BMSCs).[Methods] This study recruited 20 healthy controls with normal bone marrow picture and 20 patients with psoriasis vulgaris,including 10 at progressive stage and 10 at resting stage.The psoriasis area and severity index (PASI) score varied from 0.6 to 22.8 and averaged 10.97 in these patients.Bone marrow mononuclear cells were isolated by density-gradient centrifugation from bone marrow of these subjects,and BMSCs were cultured with adherent method.After three passages,the BMSCs were subjected to a 72-hour culture followed by the identification of cell phenotypes via flow cytometry and determination of TGF-β1,SCF,KGF and TNF-α levels in the culture supernatant via enzyme linked immunosorbent assay (ELISA).The parameters were compared by two independent samples t test between the two groups,and the correlation of eytokines with PASI was assessed by Pearson correlation analysis.[Results] Inverted microscopy revealed no obvious difference in the morphology of BMSCs between the patients and controls.CD29 was expressed by more than 90％ of the BMSCs,but no expression of CD45,CD34 or HLA-DR was observed in them.The BMSCs from patients showed a significantly lower level of supematant TNF-α ((22.93 ± 10.1 1 ) μg/L vs.(35.73 ± 15.15) μg/L,t =3.14,P ＜ 0.05),a higher level of supernatant SCF ((76.80 + 16.19) μg/L vs.(59.86 + 22.41) μg/L,t =2.74,P＜ 0.05),and asimilar level of supernatant KGF and TGF-β1 (both P＞ 0.05) compared with those from the controls.The PASI score was uncorrelated with the levels of SCF,TNF-α,KGF or TGF-β1 secreted by BMSCs in patients with psoriasis (all P＞ 0.05).[Conclusion]s The levels of SCF and TNF-α secreted by BMSCs are aberrant in patients with psoriasis,hinting an abnormal bone marrow microenvironment in these patients.
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Objective To study the expressions of Notch receptors (Notch1 and 2) and target gene Hes-1 in bone marrow CD34+ cells from patients with psoriasis. Methods CD34+ cells were isolated from the bone marrow of 12 patients with psoriasis and 19 normal human controls. Western blot was conducted to detect the expressions of Notchl, Notch2 and Hes-1 proteins in CD34+ cells, with the house-keeping gene β-actin as an internal reference. Results In contrast with normal controls, a significant increment was observed in the expressions of Notch1 and Hes-1 proteins in psoriatic patients (0.9488 ± 0.3221 vs. 0.6693 ± 0.1465, 0.8579 ±0.3729 vs. 0.5728 ± 0.1787, both P ＜ 0.05). No significant difference was observed in the expression of Notch2 between psoriatic patients and normal controls (0.7568 ± 0.3461 vs. 0.8312 ± 0.2887, P ＞ 0.05).Conclusion The overexpression of Notch1 and Hes-1 may be associated with the low proliferation activity of psoriatic hematopoietic cells.
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Objective:To study of isolating culture and differentiation of human bone marrow-derived mesenchymal stem eeUs into blood vessel endothelial-like cells in a specialized micro-environment in vitro,SO as to provide an experimental foundation for psoriasis.Methods:The hMSCs were isolated by density gradient centrifugation,amplificated and identificated in vitro.Vascular endothelial growth factor (VEGF)and basic fibroblast growth factor(bFGF)within endothelial cell growth medium(DMEM)were used to induce hMSCs differentiation into vascular endothelial-like cells.The induced hMSCs were detected by flow cytometry to find whether they had endothelial cell phenotypes.The Dil-ac-LDL ingestion assay Was used to apprmses the blood vessel endothelial-like cell function.Results:In cell morphology,the induced hMSCs transformed into endothelial-like cells.These cells expressed specific surface markers of,Vascular endothelial-like cells such as CD34,CDl06,HLA-DR,CD54,VWF,CD31,KDR and CD5 comparing to those in the control group(P＜0.01).The induced endothelial-like eeHs had the ability of ingesting Dil-ac-LDL.Conclusion:Combination of Density gradient eentrifugation and adherent methods can obtain pure MSCs.hMSCs Can obtain endothelial cell phenotypes after induced by VEGF and bFGF in vitro.Human hnSCs have potential to differemiate into vascular endothelial-like cells.The induced endothelial-like cells have completely mature endothelial cell functional properties.
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0.05). CONCLUSION: Both modified Dexter method and IMDM medium method can promote the adherence and proliferation of bone marrow stromal cells in a short time. It is the simple and practical culture method of bone marrow stromal cells by culturing the cells in the medium of IMDM compared to the modified Dexter method.
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BACKGROUND:It is discovered in our preliminary study that the activity of psoriatic bone marrow hematopoietic cells is abnormal.OBJECTIVE:To reveal level of stem cell factor(SCF) and granulocyte colony-stimulating factor(G-CSF) secreted by bone marrow stromal cells in psoriasis patients.DESIGN,TIME AND SETTING:This case-control observation experiment was performed at the Laboratory of Department of Dermatology,Taiyuan Central Hospital from October 2007 to August 2008.PARTICIPANTS:Twenty-four common-psoriasis outpatients were selected at the Department of Dermatology,Taiyuan Central Hospital,including 16 males and 8 females,aged 16-59 years old.Twenty controls were selected from Department of Hematology,Taiyuan Central Hospital,whose age and gender were matched with psoriasis patients.METHODS:Bone marrow mononuclear cells were isolated from psoriasis patients and controls using the density gradient centrifugation.Bone marrow stromal cells were cultured by the adherent method.When the cells were cultured for three passages and 72 hours,bone marrow stromal cells and supernatant liquid were collected.MAIN OUTCOME MEASURES:The phenotypes of cells were identified by flow cytometry and the level of SCF and G-CSF were detected by enzyme linked immunosorbent assay kit(ELISA).RESULTS:Flow cytometry assay showed that over 90% bone marrow stromal cells were positive for CD29,but negative for CD34,CD45 and HLA-DR.That is,the purity of bone marrow stromal cells was over 90%.The levels of SCF and G-CSF in psoriasis patients were significantly higher than that in controls(P
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2?mol/L) was obvious and the inhibitive degree was nearly 100% when the concentrations of arsenic trioxide and cisplatin were 12?mol/L and 4?mol/L. 2.Higher concentrations of arsenic trioxide and cisplatin perturbed cell through S-phase and up-regulated p53 gene expressions.Conclusions The inhibitive effect of arsenic trioxide combined with cisplatin was more obvious than either one used separately; the apoptosis mechanism of ovarian cancer cell line HO-8910 is related with perturbing of S phase and up-regulating of p53 gene expression.
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Objectives: To study the prolonging of mandible by distr ac tion osteogenesis (DO) after severe trauma in rabbits. Methods:O steotomy was conducted in 16 adult rabbits. To simulate severe trauma,periosteum was removed and inferior alveolar vessels were destroyed on left side. The rabb its were randomly divided into 4 groups with 4 in each group and internal distra ctor was applied in each rabbit. In group A1 and A2 the latency time was 1 day,i n group B1 and B2 that was 7 days.In group A1 and B1 the distraction velocity wa s 0.5 mm/d,in group A2 and B2 that was 1.0 mm/d.The distraction length was 10 mm and retention period was 4 weeks. Results:4 weeks after operati on on right side complete new bone formation was found in the distraction area. On left side that was observed in group B1 and B2,but not in A1 and A2.Nonunion was found in 1,4,0 and 0 cases in group A1,A2,B1 and B2 respectively.The bending strength (10 4 N/m 2) of normal bone was 95,that in group A1,B1,B2 was 25,85 and 60 respectively. Conclusion:DO method can be used even after the blood supply of the mandibles has been destroyed, but the latency period sh ould be longer.
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To investigate the mechanism of common carotid artery injury produced by explosion in neck region, and to determine the severity of carotid injury based on the injury of neck and the pressure of blast waves. After the detonation of the blast source at different distances, the injuries to rabbits' neck and carotid artery were examined, and the pressure of the blast waves to both skins and common carotid artery were measured with PVDF(polyvinylidene fluoride)sensors and oscilloscope. The endothelium of the injured carotid artery desquamated and micro thrombus formed on the arterial walls the after injury. Disruptions in the tunica media might account for pseudo aneurysm formation. These results offered experimental evidences pseudo aneurysm and thrombus formation in the carotid artery after an explosion in the neek region.