Adult ; Aged ; Aged, 80 and over ; Buruli Ulcer ; pathology ; surgery ; DNA, Bacterial ; analysis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mycobacterium ulcerans ; genetics ; isolation & purification ; Tuberculosis, Cutaneous ; pathology

ObjectiveTo observe effect of OT training on patients wearing the upper limd prosthesis. MethodsThe effect of OT to 30 patients with upper arm prosthesis was analyzed using FIM score before and after training. ResultsAfter 1-3-month OT training, the patients' FIM score were improved significantly(P<0.01).Conclusions OT is an effective method on the patients wearing upper arm prosthesis.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast ; pathology ; Breast Neoplasms ; drug therapy ; pathology ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; drug therapy ; pathology ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; pathology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Sarcoma ; pathology ; Spleen ; pathology ; Splenic Neoplasms ; drug therapy ; pathology ; Vincristine ; therapeutic use

In order to enhance the specificity of TNF-α monoclonal antibody to inflamed site, a bispecific antibody BsDb that targets TNF-α and the extra-domain B (ED-B) of fibronectin (FN) was constructed by covalently linking the anti-TNF-α single chain Fv antibody (TNF-scFv) and the anti-ED-B scFv L19 via a flexible peptide linker deriving from human serum albumin (HSA). ED-B is an antigen specifically expressed at the inflamed site. BsDb is expressed in E. coli, identified by immunoblot, and purified with affinity chromatography. This was followed by further examination of its bioactivities and pharmacokinetics. We demonstrated that BsDb retained the immunoreactivity of its original antibodies as it could simultaneously bind to TNF-α and ED-B and neutralize the biological action of TNF-α. In the collagen-induced arthritis mice model, BsDb selectively accumulate in the inflamed joint with a maximal uptake of (12.2 ± 1.50)% ID/g in a single inflamed paw and retain in the inflamed paw for at least 72 h. In contrast, BsDb showed a short serum half-life of (0.50 ± 0.05) h and a rapid clearance from normal tissues. The findings reported herein indicate that BsDb has good specificity to the inflamed site and low toxicity to normal tissues. BsDb is therefore likely to have greater clinical applications in the treatment of rheumatoid arthritis and other autoimmune diseases. This laid a stable basis for its preclinical study.
Animals ; Antibodies, Bispecific ; chemistry ; Antibodies, Monoclonal ; chemistry ; Arthritis, Experimental ; Escherichia coli ; Fibronectins ; chemistry ; Half-Life ; Humans ; Mice ; Single-Chain Antibodies ; chemistry ; Tumor Necrosis Factor-alpha ; chemistry

Child, Preschool ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 8 ; Chromosomes, Human, Pair 9 ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Translocation, Genetic

OBJECTIVE Diabetes-induced endothelial cell (EC) dysfunction and neovasculariza-tion impairment constitute vascular complications with limited treatment regimens.Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic role in progression of diabetes.The pres-ent study was designed to determine the involvement of FOXO1 in impaired EC function and post-isch-emic neovascularization in diabetes and investigate underlying mechanisms.RESULTS We found that FOXO1-selective inhibitor AS1842856 improved blood flow recovery and capillary density in ischemic hindlimb,and rescued the delay of wound closure with a concomitant augmentation of mean perfusion rate in diabetic mice. In vitro,treatment with AS1842856 or FOXO1 siRNA abrogated high glucose-in-duced apoptosis and ameliorated capillary tube formation in human umbilical vein endothelial cells(HU-VECs). FOXO1 inhibition relieved alterations in mitochondrial networks and significantly suppressed the over production of mitochondrial reactive oxygen species(mtROS)induced by high glucose in ECs. Expression of dynamin-relatedprotein-1 (Drp1) and phosphorylation at Ser616, a protein required for mitochondrial fission, were enhanced by hyperglycemia, which could be neutralized by FOXO1 inhibition. Moreover, the transcription of Rho-associated coiled-coil containing protein kinase 1 (ROCK1), which phosphorylates Drp1 at Ser616, was shown by luciferase assay to be directly regulated by FOXO1. CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and func-tion in ECs,and FOXO1 may serve as a therapeutic target for microvascular complications of diabetes.

Objective To investigate the removal effect of immunoadsorption (IA) on associated antibodies and the efficacy in late-onset myasthenia gravis (MG). Methods A total of 25 late-onset MG patients were randomly selected to enroll in this study. IA therapy was given to 10 patients (IA group), while immunoglobin (0.4 g·kg-1·d-1) was administrated to the other 15 patients for 5 days(Ig group). The titers of Titin antibody (Titin-ab), acetylcholine receptor antibody (AchR-ab) and presynaptic membrane antibody (PrsmR-ab) were detected before and after the treatment. Quantitive MG (QMG) score was assessed before and immediately after the entire course of treatment. The clinical efficacy, the duration of respiratory support and in-hospital were compared between two groups. The correlation between three antibodies and QMG score was also analyzed. Results Compared with that before treatment, the Titin-ab PIN values, the AchR-ab PIN values, and the PrsmR-ab P/N values of IA group were all decreased significantly after treatment (P<0.05, respectively). The P/N value of Titin-ab in IA group was decreased by 54.7%～3.5%, which was significantly higher than that in Ig group(19.9%±3.1%) (P<0.01). QMG score reduced by 42.4%± 4.2% and 23.8%±3.7% in IA group and Ig group respectively (P<0.01, respectively). Symptoms were effectively ameliorated by both treatments, but the effective power of IA group was higher than that of Ig group (70% vs 40%, P<0.05). Remission time of IA group was significantly shorter than that of Ig group [(5.38±0.42) d vs (8.4±1.54) d, P=0.008), so was the duration of in-hospital [(13.50±0.50) d vs (16.50±0.50) d, P<0.05). The number of respiratory support in IA group was less than that in Ig group (1/10 vs 6/15, P<0.05). By the Pearson correlation analysis, the decrease of Titin-ab showed a better longitudinal correlation with the decrease of QMG score than the other two antibodies (r=0.6315, P<0.01). Conclusion IA can rapidly and effectively clear the pathogenic antibodies of late-onset MG patients and its short-term clinical efficacy is better than immunoglobin.

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

Objective To study the exocrine pancreatic function in critically ill children with septic shock,sepsis and hyperlactacidemia.Methods A total of 64 critical pediatric patients were admitted from Jan 2009 to Oct 2012,and clinical and laboratory findings including pancreatic function,and histopathological features and score after autopsy were reviewed.Results (1) Compared with non-septic shock children,the pancreatic pathology score and serum lipase in septic shock group were significantly higher and serum calcium was significantly reduced (P ＜0.05) ; (2) The pancreatic histopathology score was significantly increased in patients with elevated plasma lactate ≥2 times (P ＜0.05),but there were no significant differences in serum calcium and blood amylase and lipase between patients with elevated plasma lactate level and patients with normal plasma lactate level; (3) The concentrations of serum amylase,lipase and urinary amylase were significantly increased in patients with pancreatic histopathology score ＞4 points compared with score ≤4 points patients,but there were no significant differences in above three biomarkers between patients with score ≤3 points and patients with score ＞3 points.Conclusions The pancreas is vulnerable to damage easily occurred in septic shock children especially complicated with hyperlactacidemia.The pancreatic histopathology score ＞ 4 points can be as a sensitive and reliable indicator of pancreas damage.

Objective To observe the safety and efficacy of preoperative Ticagrelor loading in emergency percutaneous coronary intervention (PCI)for acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 213 patients with acute STEMI before undergoing emergency PCI were randomly divided into Ticagrelor group(n =105)receiving 180 mg Ticagrelor loading dose,then 90 mg twice daily and Clopidogrel group(n =108) receiving 600 mg of Clopidogrel,then 75 mg once daily.Emergency PCI postoperative coronary artery TIMI flow grade and the change of incidence of no reflow,platelet aggregation rate,incidence of bleeding events and the incidence of major adverse cardiovascular events(MACE) were compared between two groups.Results The rate of no-reflow was 7.6 ％ (8 cases)in Ticagrelor group,and 16.7 ％ (18 cases) in Clopidogrel group(x2 =3.26、P=0.030).Platelet aggregation rates at 1 h and 24 h after treatment were (55.6±4.3)％ and (48.6 ± 4.1) ％ respectively in Ticagrelor group,and (63.6 ± 3.8) ％ and (57.6 ± 3.6) ％ respectively in Clopidogrel group,which showed that platelet aggregation inhibition effect was better in Ticagrelor than in Clopidogrel (t =14.40、17.20,both P =0.001).Two groups had no major life-threatening bleeding events.Bleeding incidence had no statistically significant difference between two groups(x2 =0.14,P =0.710),and the incidence of cardiovascular adverse events showed no statistically significant difference(x2 0.04,P 0.840)between the 2 groups.Conclusions Preoperativeticagrelor loading treatment in emergency PCI therapy for acute ST segment elevation myocardial infarction shows stronger antiplatelet aggregation function,significantly improve postoperative TIMI flow,and does not increase the incidence of bleeding events.