The aim of the study is to determine the characteristics of the material properties of various structures in the temporomandibular joint (TMJ) and the mandibular bone tissues in nanoscopic scale. Using the atomic force microcopy (AFM) with the nanoindentation method, the nanomechanical properties of 6 discs, condylar cartilages and fossate cartilages in the TMJ, and 6 cortical and cancellous bones in the mandible of 3 normal adult men, were measured and analyzed. Results showed that marked differences were found in elastic properties among the different regions of the disc, articular cartilage in the TMJ. In the distribution of elastic modulus in these various structures, the elastic modulus was higher in the anterior and medial regions and lower in the middle, posterior and lateral regions. Otherwise, elastic modulus of the cortical bone in the mandible was approximately 2 times more than the cancellous bone. Elastic modulus in the buccal bone tissues of the mandible was more distinctly below one of the lingual site. The results suggested that the disc, condylar cartilage and fossate cartilage in the TMJ and the cortical and cancellous bone in the mandible were inhomogeneous with the nanolevel measurement. Different structures or various regions in the same structure were loaded by different local mechanical forces in the nanoscale.

Objective To examine the brain metabolic changes in WD patients receiving copper chelation by us?ing 1H-MRS. Method Thirty-nine patients with WD was randomly divided into four groups: non-brain type group (18 cases), brain type prior-treatment group and short-term treatment group (21 cases), long-term treatment group (20 cases) from short-term treatment group, and 20 healthy volunteers served as a control group. 1H-MRS and MRI were performed on patients on 1.5/MR/MRS system to detect these above-mentioned items before and after treatment. Result The mean of NAA/Cr was significantly lower in the left putamen and head of the caudate nucleus than in the left basal ganglion in the 39 patients with WD. The mean of NAA/Cr and Cho/Cr in the left putamen and basal ganglion was significantly lower in non-brain type group than in control group(P<0.01). The mean of NAA/Cr Cho/Cr and NAA/Cho in the left putamen,head of the caudate nucleus and basal ganglion were significantly lower in brain type group than in control group(P<0.01 or P<0.05). The mean of NAA/Cr in the left putamen was much lower in brain type group than in non-brain type group (P<0.01). The mean of NAA/Cr, Cho/Cr and NAA/Cho of short-term treatment group in the left putamen, head of the caudate nucleus and basal ganglion was not significantly different between brain type group and short-term treatment group(P>0.05). The mean of NAA/Cr and NAA/Cho in the left putamen and basal ganglion was much higher in long-term treatment group than in brain type group(P<0.01 or P<0.05). The mean of Cho/Cr in the left head of caudate nucleus were much higher after treatment compared with prior-treatment group(P<0.05). The mean of NAA/Cr in the left putamen, head of the left caudate nucleus and basal ganglion in all groups was negatively correlated with course of the disease. Conclusion There are significant differences in brain metabolism among different type of WD. The long-term but not short-term copper chelation significantly improves brain metabolism. NAA/Cr may be used as a non-invasive indicator to examine the efficacy of treatment.

OBJECTIVETo explore the application of serum protein pattern models in diagnosis of colorectal cancer (CRC) by proteinchip technology.

METHODSOne hundred and forty-seven serum samples (55 CRC patients and 92 healthy individuals) randomly divided into training set (n = 87, 32 CRC patients and 55 healthy individuals) and test set (n = 60), were subjected for analysis by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Four top-scored peaks in 5910, 8930, 4476 and 8817 were detected by proteinchip software version 3.0. and were trained by a multi-layer artificial neural network (ANN) with a back propagation algorithm. An artificial neural network classifier had developed for separating CRC from the healthy group. The classifier was then challenged with the test set (60 samples including 23 CRC patients and 37 healthy individuals) to determine the validity and accuracy of the classification system.

RESULTSThe artificial neural network classifier separated the CRC from the healthy samples, with sensitivity of 82.6% and specificity of 91.9%.

CONCLUSIONCombination of SELDI-TOF-MS with the artificial neural network yields significant higher sensitivity and specificity than CEA in the diagnosis of CRC, which should be further studied.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; analysis ; Blood Proteins ; analysis ; Colorectal Neoplasms ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Neural Networks (Computer) ; Protein Array Analysis ; Proteomics ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To construct the adenoviral vector with co-expressing keratinocyte growth factor (KGF) and enhanced green fluorescent protein (EGFP) for transfection into the mesenchymal stem cells (MSC), the target gene KGF was cloned into the shuttle plasmid with the report gene EGFP, then the recombinant shuttle plasmid was transformed into DH5a bacteria to recombine with backbone vector pAdxsi. Next, the plasmid pAd-EGFP-mKGF was amplified in H293 cells and the viral titer was determined. The MSC were separated and enriched by using bone marrow adherent culture and identified in vitro to observe the efficiency of transfection. The results indicated that the recombinant shuttle plasmid pShuttle-EGFP-mKGF digested with restriction endonucleases was confirmed by two products which length was about 0.6 kb and 5.1 kb, respectively; the recombinant plasmid pAdxsi-EGFP-mKGF digested with restriction endonucleases was confirmed by 7 products; recombinant adenoviral vector Ad-EGFP-mKGF was amplified to titer of 1.6 × 10(10) pfu/ml. At 10 h after transfecting MSC began to express fluorescence at 6 to 8 days later, the fluorescence reached to the peak with infection rate of 92.3, at 28 days the expression of fluorescence was still observed. It is concluded that the recombinant adenoviral vector Ad-EGFP-mKGF is successfully constructed and can transfect MSC effectively and safely.
Adenoviridae ; genetics ; Animals ; Bone Marrow Cells ; cytology ; Fibroblast Growth Factor 7 ; genetics ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Male ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Plasmids ; Transfection

OBJECTIVETo observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.

METHODSFrom June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.

RESULTSThe mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).

CONCLUSIONOur results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

Calcineurin Inhibitors ; Female ; Heart Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; therapeutic use

OBJECTIVETo explore immunoregulatory mechanism of mesenchymal stem cells (MSCs) in H-2 haploidentical bone marrow cells transplantation mice.

METHODSBALB/c female mice irradiated with 8Gy 60Co gamma-rays were divided into two groups: MSCs group, infused cm-DiI labeled MSCs from female CB6F1 mice and monocytes from the bone marrow and spleen of male CB6F1; Control group, only infused monocytes from the bone marrow and spleen of male CB6F1. T-lymphocyte subpopulation of peripheral blood cells, T and B cells proliferation stimulated by ConA and LPS, mixed lymphocyte reaction between donor and recipient and third part, the sry-gene chimerism of bone marrow, spleen and thymus of the recipient, the distribution of MSCs in the recipient, the incidence rate of GVHD and survival were observed.

RESULTSThe CD3 at +90 d the percent of CD3+ CD4+ cells, and CD4/CD8 at +30 d in the MSCs group were higher than that in control post-transplantation, respectively (P < 0.05). The proliferation activity of B cells recovered more rapidly and that of T cells recovered comparably in MSCs group as compared with that in control group. The result of MLR between donor and recipient was lower in MSCs group than that in the control; and that between recipient and the third part had no difference. The sry-gene chimerism of bone marrow and spleen of the recipient was higher in MSCs group than in control at +30 d. The MSCs mainly distributed in intestine, thymus, bone marrow, liver, heart of the recipient after transplantation. The incidence of acute GVHD was higher and the survival rate was lower in MSCs group than that in control group (P < 0.05). Chronic GVHD occurred in the control group at +90 d, while in the MSCs group at +120 d.

CONCLUSIONSMSCs might improve stem cell engraftment, promote lymphocyte and humoral immunity recovery, decrease incidence of GVHD and increase survival by inducing specific immunologic tolerance and repairing organs injuries.

Animals ; Bone Marrow Cells ; immunology ; Bone Marrow Transplantation ; immunology ; Female ; Graft vs Host Disease ; immunology ; Male ; Mesenchymal Stromal Cells ; immunology ; Mice ; Mice, Inbred BALB C

This study was purposed to analyze the clinical characteristics of multiple myeloma (MM) patients with and without renal impairment (RI) and to investigate the effect of bortezomib (Bor) on MM with RI. Clinical data of 39 MM patients (15 cases with RI, 24 cases without RI) received treatment of Bor in department of hematology in our hospital from Jan 2007 to Aug 2011 were collect and analyzed in term of clinical characteristics, curative efficacy, outcome of renal impairment and toxic reaction associated to chemotherapy. The results showed that (1) the obvious difference of the disease type, the creatinine, uric acid, serum calcium and β2-microglobulin levels existed in patients with and without RI, while there were no significant difference in hemoglobin and globin levels; (2) there were no significant difference in overall reaction rate and overall survival rate between MM patients with and without RI, however the median survival time of patients without RI was longer than that of patients with RI; (3) the RI could be reversed after the treatment with Bor, and the effect was most obvious after the first cycle. 20% MM patients with RI had recovered from RI after the first cycle; and the recovery rate from RI got up to 38.4% after the second cycle. The decline of creatinine levels had no difference between MM patients with or without RI after the second cycle. (4) The adverse events included gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia and infection. There was also no difference between the 2 groups. It is concluded that Bor-based regimens for the MM patients with RI are effective and safe, and the renal function would be reversed after 2 cycle of Bor-based regimen.
Adult ; Aged ; Aged, 80 and over ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; physiopathology ; Pyrazines ; adverse effects ; therapeutic use ; Renal Insufficiency

The aim of this study was to investigate the clinical situation of invasive fungal infections in patients with hematological malignancies, and discuss the susceptible factors and precautions. 541 patients with hematological malignancies from 2008 Jan to 2011 Dec in hospital 307 of Chinese PLA were statistically retrospectively analyzed in term of clinical manifestation, image examination, culture results of secretions, therapy and so on. The results showed that 63 out of 541 patients got invasive fungal infections. The respiratory tract and intestinal tract were the most common infection sites (62.34 and 19.48, respectively); Candida albicans (66.67) and Candida glabrata (12.82) were the most common pathogens. It is concluded that the main risk factors are as follows: primary diseases, chemotherapy, glucocorticoid, leukopenia after chemotherapy, applications of broad-spectrum antibiotics and aging. It is suggested that a stratification of risk factors is helpful in preventing and treating invasive fungal infections.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Candida ; pathogenicity ; Child ; Cross Infection ; microbiology ; Female ; Hematologic Neoplasms ; complications ; microbiology ; Humans ; Male ; Middle Aged ; Mycoses ; complications ; microbiology ; Retrospective Studies ; Young Adult

This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy γ-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.
Animals ; Cell Cycle ; drug effects ; radiation effects ; Female ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Thymocytes ; drug effects ; radiation effects

The aim of this study was to investigate effects of IAT and MAT chemotherapeutic regimens treating patients with refractory and relapsed acute myeloid leukemia (AML). 99 patients with refractory and relapsed AML received IAT regimen or MAT regimen as study objects were retrospectively analyzed (56 patients with refractory AML and 43 patients with relapsed AML). Among of them, 28 patients were treated with IAT regimen, and 71 patients received with MAT regimen. The results showed that in 2 groups mentioned above the OR was 65.7%, CR was 49.5%, PR was 16.2%; in IAT group the OR was 64.3%, CR was 46.4%; in MAT group the OR was 66.2%, CR was 50.7%, no statistical difference was found between these 2 groups; The 2 years overall survival was 25% in IAT group and 15.5% in MAT group. Serious infection in IAT and MAT regime groups was 25% and 9.9%, respectively. It is concluded that both IAT and MAT regimens are effective methods for inducing CR in patients with refractory of relapsed AML. IAT and MAT regimens can be used in treatment of the refractory or relapsed MAL patients who were not respond to other regimen.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; etiology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Vidarabine ; administration & dosage ; Young Adult