BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.

METHODSHHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.

RESULTSThe average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.

CONCLUSIONSThalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.

Animals ; Animals, Genetically Modified ; Female ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic ; drug therapy ; metabolism ; Thalidomide ; therapeutic use ; Transforming Growth Factor beta3 ; genetics ; Vascular Endothelial Growth Factor A ; metabolism ; Zebrafish

The aim of this study was to investigate the biological characteristics of human bone marrow mesenchymal stem cells from bone marrow of different age donors. The experiments were divided into four groups by donors age, group A represented MSC derived from fetal bone marrow, group B represented MSC derived from bone marrow of 0-20 years old donors, group C represented MSC derived from bone marrow of 20-40 years old donors and group D represented MSC derived from bone marrow of donors older than 40. The growth, purification, proliferation and multipotential abilities of MSC in 4 groups were observed and their immunophenotypes were determined by flow-cytometry. The level of cytokines (IL-6, SCF, FLT-3L, SDF-1 and TGF-beta1) were assayed by ELISA method. Cell cycles were analyzed to show the proliferation index (PrI). MSCs derived from bone marrow of 4 groups were injected subcutaneous into NOD/SCID mouse to observe the safety. The results showed that different age donors bone marrow all gave rise to MSC. These cells were similar in morphology, antigenic phenotype, differentiation potential and cell cycle. The primary culture time of group B was shorter than other groups. The duration of passage 1 (P1) was 5.5 days, and the duration of P10 was 33 days, after P10 culture, (5.19 +/- 2.15) x 10(10) MSCs were obtained from 8 x 10(6) MNC of this group. The primary culture time of groups A, C, D were longer, the duration of P1 were 15, 7 and 13 days for group A, C and D respectively, and the duration of P10 was 50, 60 and 72 days for group A, C and D, respectively. After P10 culture, (4.98 +/- 2.08) x 10(10), (1.86 +/- 0.47) x 10(10), (0.64 +/- 0.22) x 10(10) MSCs were obtained from 8 x 10(6) MNC of group A, C and D respectively. The morphology of MSC of group A was longer and slender. The ability of expansion decreased after P15 for A group, P10 for B group and P8 for C and D groups. The levels of SCF, FLT3-L, IL-6 and SDF-1 in group B were higher than other groups. Karyotype analysis showed that MSCs from 4 groups were normal, and tumor-like tissues were not developed after cultured MSCs were inoculated in NOD/SCID mice. It is concluded that there was relationship between age and the biological characteristics of human bone marrow mesenchymal stem cells. For clinical use, especially in hematopoietic stem cell transplantation (HSCT), 0-20 years old donors were perfect MSCs donors who can provide sufficient MSCs in relatively short times. MSCs of group B can be used as stem cell source because the biological characteristics of MSCs of groups B are superior to that of other groups.
Adolescent ; Adult ; Age Factors ; Animals ; Blood Donors ; Bone Marrow Cells ; cytology ; immunology ; metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Child ; Child, Preschool ; Cytokines ; analysis ; Enzyme-Linked Immunosorbent Assay ; Fetus ; Flow Cytometry ; Humans ; Immunophenotyping ; Infant ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; immunology ; metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Transplantation, Heterologous

OBJECTIVEImpulsivity is one of the core symptoms of children with attention deficit hyperactivity disorder (ADHD). In order to understand the neuromechanism of the impulsive behaviors in ADHD children, this study investigated the specific functional areas of the brain by functional MRI.

METHODSThe subjects consisted of 10 ADHD children with impulsivity, 7 ADHD children without impulsivity and 9 normal children. A functional MRI examination was performed when the subjects were instructed to finish GO and STOP tasks with the GO-STOP impulsivity paradigm. The MRI data during the two tasks of GO and STOP were averaged and the corresponding activation regions between groups were compared.

RESULTSThe data from the GO task revealed that the main activation regions of the normal children included frontal pole (superior frontal gyrus, middle frontal gyrus and medial frontal gyrus); the main activation regions of ADHD children without impulsivity were cerebellum (posterior lobe and anterior lobe bouton) and cingulated gyrus; those of ADHD children with impulsivity were medial globus pallidus and insula. The data from the STOP task showed that the main activation regions of normal children included superior frontal gyrus and middle frontal gyrus; those of ADHD children without impulsivity were middle frontal gyrus and cingulate gyrus; those of ADHD children with impulsivity were uncus and putamen. The activation regions of ADHD children with impulsivity were much fewer than the other two groups.

CONCLUSIONSThe behavior of impulsivity-control involves a number of specific functional areas in the cerebral cortex. Compared with normal children, ADHD children without impulsivity have weaker brain function and brain activation, and ADHD children with impulsivity demonstrate much fewer brain activation regions, worse brain function and little awareness of the cerebral cortex.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; physiopathology ; Brain ; physiopathology ; Child ; Humans ; Impulsive Behavior ; physiopathology ; Magnetic Resonance Imaging ; Male

OBJECTIVE: To investigate the clinical application of percutaneous vertebroplasty (PVP). METHODS PVP was performed in 21 cases of 37 vertebral lesions,including 14 osteoporotic compression fractures, 6 metastases, 1 hemangioma,and 17 lesions in thoracic vertebra and 20 in lumbar. The procedures of PVP were as follows: The needle was inserted via percutaneous transpedicular approach or percutaneous posterolateral vertebral approach; the needle tip was placed at the junction of the anterior located the one third of the vertebral body; intraosseous venography was performed; and last bone cement was injected at 2-10 mL. The technical success rate, clinical efficacy and complications were observed after the procedure. Results The procedure was successful in 18 cases with 31 lesions,and the success rate according to the number of cases and vertebral lesions was 85.7% (18/21) and 83.8% (31/37), respectively. After the procedure, the numbers of complete remission, partial remission, mild remission and no remission were 10, 5, 2 and 1, respectively; and the total effective rate was 94.4% (17/18). Progressive compression did not occur. Three patients had transient neuropathy and recovered after physiotherapy. Other complications were insignificant; no severe complications occurred. Conclusion PVP is an effective and micro-traumatic treatment for patients with benign and malignant lesions in vertebral bodies.
Adult ; Aged ; Female ; Fractures, Compression ; surgery ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Orthopedic Procedures ; methods ; Osteoporosis ; complications ; Spinal Fractures ; etiology ; surgery ; Thoracic Vertebrae ; surgery

OBJECTIVETo investigate the influence of high-voltage electrical burn (HEB) on the aggregation and adhesion of platelet and leukocyte in rats and the interventional effect of pentoxifylline (PTX).

METHODSOne hundred and eighty SD rats were divided into control, electrical burn (EB), and pentoxifylline treatment (PT) groups according to the random number table, with 60 rats in each group. (1) Ten rats were taken from each group at 15 minutes before injury for the observation of the microcirculatory perfusion of chest skin with Laser Doppler Perfusion Imager (LDPI), and the number of leukocyte adherent to mesenteric venule with Bradford Variable Projection Microscope (BVPM). Serum was collected from heart blood to determine the contents of platelet activating factor (PAF), thromboxane B2 (TXB2), prostacyclin (PGI2), P-selectin, E-selectin and L-selectin by double-antibody sandwich enzyme-linked immunosorbent assay. The ratio of TXB2 to PGI2 was calculated therefrom. (2) Model of HEB was reproduced in the remaining 50 rats of EB group and that of PT group with voltage regulator and experimental transformer (the electrical current applied to the left forelimb and exited from the right hind limb). The remaining 50 rats of control group were sham injured with the same devices without electric current. Within 2 minutes post injury (PIM), rats in control group and EB group were intraperitoneally injected with 2 mL isotonic saline, while rats in PT group were intraperitoneally injected with 2 mL pentoxifylline (50 mg/mL). At PIM 5 and 1, 2, 4, 8 hour(s) post injury (PIH), 10 rats of every group were randomly chosen at each time point for the observation of the microcirculatory perfusion of chest skin and the number of leukocytes adherent to mesenteric venule through the same method as used above, and the levels of the related factors of aggregation and adhesion of platelets and leukocytes were determined, and then the relative ratio was calculated. Data were processed with the analysis of variance of factorial design and LSD test.

RESULTSThe contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, and the ratio of TXB2 to PGI2, as well as the number of adhered leukocyte in EB group were higher, while the microcirculatory perfusion value was lower than those of control group, with F values from 854.20 to 8156.52, P values all below 0.01. The microcirculatory perfusion value and PGI2 content of PT group were higher, while the contents or number of other indexes were lower than those of EB group, with F values from 33.18 to 1033.99, P values all below 0.01. Only the data within EB group and PT group were comparable. The contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, and the ratio of TXB2 to PGI2, as well as the number of adhered leukocyte in EB group and PT group at each time point were significantly higher than those at 15 minutes before injury, while the microcirculation perfusion value was significantly lower than that at 15 minutes before injury (P values all below 0.001), with the exception of the ratio of TXB2 to PGI2 in PT group and E-selectin in EB group and PT group at PIM 5. The contents of PAF, TXB2, and E-selectin and the ratio of TXB2 to PGI2 in EB group peaked at PIH 4, and they were respectively (9.3 ± 0.9) ng/mL, (14.31 ± 0.65) nmol/mL, (271.2 ± 18.4) ng/mL and 4.62 ± 0.26. The contents of PGI2 and P-selectin, and the number of adhered leukocyte in EB group peaked at PIH 8, and they were respectively (3.98 ± 0.24) nmol/mL, (514 ± 24) ng/mL, and (25.50 ± 4.14) per 100 µm venule. The content of L-selectin peaked at PIH 2 [(876 ± 54) ng/mL]. The microcirculatory perfusion value was lowest at PIM 5 [(1.17 ± 0.10) V].

CONCLUSIONSHEB can increase the contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, the ratio of TXB2 to PGI2, and the number of adhered leukocyte, as well as decrease the skin microcirculatory perfusion value. PTX can inhibit the aggregation and adhesion of platelets and leukocytes through increasing the content of PGI2 and decreasing contents of other factors mentioned above, thus alleviating the microcirculatory dysfunction after HEB.

Animals ; Blood Platelets ; drug effects ; Burns, Electric ; blood ; physiopathology ; Leukocytes ; drug effects ; physiology ; Male ; Pentoxifylline ; pharmacology ; Platelet Aggregation ; drug effects ; Rats ; Rats, Sprague-Dawley

BACKGROUNDInternet addition disorder (IAD) is currently becoming a serious mental health problem among Chinese adolescents. The pathogenesis of IAD, however, remains unclear. The purpose of this study applied regional homogeneity (ReHo) method to analyze encephalic functional characteristic of IAD college students under resting state.

METHODSFunctional magnetic resonanc image (fMRI) was performed in 19 IAD college students and 19 controls under resting state. ReHo method was used to analyze the differences between the average ReHo in two groups.

RESULTSThe following increased ReHo brain regions were found in IAD group compared with control group: cerebellum, brainstem, right cingulate gyrus, bilateral parahippocampus, right frontal lobe (rectal gyrus, inferior frontal gyrus and middle frontal gyrus), left superior frontal gyrus, left precuneus, right postcentral gyrus, right middle occipital gyrus, right inferior temporal gyrus, left superior temporal gyrus and middle temporal gyrus. The decreased ReHo brain regions were not found in the IAD group compared with the control group.

CONCLUSIONSThere are abnormalities in regional homogeneity in IAD college students compared with the controls and enhancement of synchronization in most encephalic regions can be found. The results reflect the functional change of brain in IAD college students. The connections between the enhancement of synchronization among cerebellum, brainstem, limbic lobe, frontal lobe and apical lobe may be relative to reward pathways.

Adolescent ; Adult ; Asian Continental Ancestry Group ; Behavior, Addictive ; epidemiology ; physiopathology ; Brain ; physiopathology ; Female ; Humans ; Internet ; Magnetic Resonance Imaging ; Male ; Young Adult

OBJECTIVETo investigate the relation between changes in serum vascular endothelial growth factor (VEGF) level after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression, especially in relation to metastasis.

METHODSSerum VEGF expression level, measured by quatitative sandwich enzyme-linked immunosorbent assay (ELISA, R&D system), was measured before, 3 days and 4 weeks after TACE in 30 patients with HCC. The development of metastasis was evaluated at the end of the third month after TACE.

RESULTS1. The serum VEGF level in 30 patients was 154.47 +/- 90.17 pg/ml, 2. Post-TACE total serum VEGF level increased as compared with their basal level in 30 patients (P < 0.05) and serum VEGF level had a tendency to increase in patients with heterogeneous uptake of iodized oil and portal vein thrombosis. During the follow-up of 1 - 2 years, metastatic foci were found in 74% (20) patients with SVEGF increase, while none of the patients showing SVEGF decrease developed metastasis.

CONCLUSIONSerum VEGF expression increase is associated with the development of metastasis in hepatocellular carcinoma after TACE.

Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; blood ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Vascular Endothelial Growth Factor A ; blood

BACKGROUNDThe diagnostic value of virtual imaging combined with three-dimensional computed tomographic angiography (3D-CTA) for intracranial aneurysms has not been fully elucidated yet. This study aimed to evaluate the value of combined application of virtual imaging techniques and 3D-CTA in diagnosing patients with aneurismal subarachnoid hemorrhage (SAH) at the acute stage.

METHODSEighty patients with non-traumatic SAH received 3D-CTA examinations. The raw CT data of these patients were reconstructed and transferred into the 3D mode through the surgical plan system based on virtual reality (VR) image, and the 3D virtual images of skulls and brain blood vessels were acquired. The location, size and shape of aneurysms and their anatomic relationship with adjacent tissues were measured from many points of view.

RESULTSSeventy-three aneurysms were detected in 68 of the 80 patients, but 2 aneurysms were detected in 2 of the 5 patients who had been found free of aneurysms previously and had received 3D-CTA examinations for a second time one month later. The 3D virtual images produced by the virtual imaging system were clear and vivid, and they could reveal the location and size of the aneurysm and its relations to the parent artery and skull directly.

CONCLUSIONSThe imaging of 3D-CTA is convenient, reliable and fast in diagnosing intracranial aneurysms and can be regarded as the first choice for the diagnosis and treatment of ruptured intracranial aneurysms. Combined with the surgical plan system based on the VR image, 3D-CTA may obtain more imaging information about aneurysms.

Adolescent ; Adult ; Aged ; Angiography ; methods ; Female ; Humans ; Imaging, Three-Dimensional ; methods ; Intracranial Aneurysm ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Tomography, X-Ray Computed ; methods ; Young Adult

OBJECTIVETo evaluate the impact of combined therapy with transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model.

METHODSBM-MSCs were obtained from pig bone marrow, expanded in vitro with a purity of > 50%. MI was induced by ligating the distal left anterior descending artery in pigs. Eighteen animals received BM-MSCs cells (5 x 10(6)/ml, n = 6), BM-MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) pfu, n = 6) or equal volume culture medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated myocardial perfusion imaging and coronary angiography were performed before and four weeks after transplantations. Histological examination was also performed 4 weeks after transplantation.

RESULTSLVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/- 6 vs. 34 +/- 3%, P < 0.05) treated animals while remained unchanged in IMDM (30 +/- 3 vs. 32 +/- 2%) treated animals 4 weeks post transplantation. Similarly, capillary density was also significantly higher and myocardial perfusion defect scores significantly decreased in BM-MSCs or BM-MSCs + HGF treated hearts than that in IMDM treated hearts. However, all these changes were similar between BM-MSCs and BM-MSCs + HGF groups. Rentrop score was similar before and 4 weeks after transplantation among various groups.

CONCLUSIONHGF in combination with BM-MSCs transplantation did not enhance the cardiac repair effects of BM-MSCs transplantation alone and BM-MSCs transplantation did not improve collateral circulation in this model.

Animals ; Bone Marrow Transplantation ; Collateral Circulation ; Disease Models, Animal ; Hepatocyte Growth Factor ; therapeutic use ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; surgery ; therapy ; Swine

OBJECTIVETo observe the clinical effect of the concentrated suture fixation method on skin transplantation on deep burn wound or wound of cicatricial deformity after burn in the jaw and neck region.

METHODSOne hundred and fourteen patients, hospitalized from April 2002 to December 2011, with deep burn or cicatricial deformity after burn in the jaw and neck region, were divided into packaging group and concentrated suture group according to the random number table. Each group had 57 patients including 48 cases with deep burn and 9 cases with cicatricial deformity. Traditional suture-package fixation method and concentrated suture fixation method were respectively used in packaging group and concentrated suture group to fix the autologous medium split-thickness skin in transplantation on wounds or scars. On post operation day (POD) 14, the skin microcirculatory perfusion flow of skin graft was measured, and the occurrence of ecchymoma, infection, and necrosis of skin in operative region were observed. The elasticity and contracture of grafted skin and scar hyperplasia on wound edge were observed 6 months after operation. Measurement data were processed with u test, while enumeration data with Fisher's exact test or Chi-square test.

RESULTS(1) On POD 14, the skin microcirculatory perfusion flow in concentrated suture group [(2.86 +/- 0.8) V] was significantly higher than that in packaging group [(2.33 +/- 0.15) V, u = 17.776, P < 0.05]. (2) Ecchymoma occurred in 4 patients of packaging group and 3 patients of concentrated suture group, but the difference between two groups was not statistically significant (chi 2 = 0.152, P > 0.05). (3) Infection in operative region was observed in 1 patient of packaging group, while no patient in concentrated suture group showed this symptom. The difference between two groups was not statistically significant (P > 0.05). (4) Grafted skin in 6 patients of packaging group showed foliated necrosis, which was not observed on those of patients in concentrated suture group. The difference between two groups was statistically significant (P < 0.05). (5) Centipede leg-like scar hyperplasia on wound edge occurred in 21 patients in packaging group and 6 patients in concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 10.920, P < 0.05). (6) Poor elasticity of grafted skin was detected in 17 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 9.865, P < 0.05). (7) Obvious contracture of grafted skin was observed in 15 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 11.684, P < 0.05).

CONCLUSIONSConcentrated suture fixation method is suitable for application in transplantation of big sheet skin on wound in the jaw and neck region. It has high survival rate and is convenient for postoperative observation.

Adult ; Burns ; surgery ; Cicatrix ; surgery ; Female ; Humans ; Jaw ; surgery ; Male ; Middle Aged ; Neck ; surgery ; Skin Transplantation ; methods ; Sutures ; Transplantation, Autologous ; Treatment Outcome