Albuminuria ; drug therapy ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Diabetic Nephropathies ; drug therapy ; Humans ; Tetrazoles ; therapeutic use

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.
Bacteriophages ; Drug Evaluation, Preclinical ; Genes, Reporter ; HEK293 Cells ; Humans ; Interleukin-6 ; metabolism ; Lipopolysaccharide Receptors ; metabolism ; Luciferases ; genetics ; metabolism ; Peptide Library ; Peptides ; metabolism ; pharmacology ; Promoter Regions, Genetic ; Protein Binding ; Signal Transduction ; drug effects ; Toll-Like Receptor 1 ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 6 ; metabolism ; Transfection ; Tumor Necrosis Factor-alpha ; metabolism

Glioma is the most common primary intracranial tumor, among which glioblastoma (GBM) is the most malignant subtype. Because of its high heterogeneity and invasiveness, GBM can't be completely removed by surgical resection and is also resistance to chemotherapy and radiotherapy. Even after a standard therapy, the median survival time is only 14.6 months, the five-year survival rate is less than 10%, and the relapse of GBM is common. Immunotherapy, a new treatment paradigm, treats cancer through regulating the autologous immune system and the tumor microenvironment. As a promising method to improve the prognosis of GBM, immunotherapy has attracted more and more attention. This paper gives a review to the difficulty, the mainly existing strategies and the bottlenecks in GBM immunotherapy, aiming at providing new direction to improve the prognosis of GBM patients.

OBJECTIVETo detect the changes of naive T cell level of thymic recent output at different stages of treatment in patients with diffuse large B-cell lymphoma (DLBCL), thereby to evaluate the relationship of thymic recent output function with prognosis and the impact of chemotherapy on the potential of immunological recovery.

METHODSThe levels of T-cell receptor rearrangement excision circles (TREC) in DNA of peripheral blood mononuclear cells (PBMNC) from 30 DLBCL patients were monitored before, during, until 3 months and 6 months after chemotherapy by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3 positive(CD3(+)) cells. Twelve normal individuals who matched in age were served as controls.

RESULTSThere was a dramatic reduction of TREC values in all DLBCL patients among which TREC values in germinal center B-cell-like-DLBCL (GCB-DLBCL) were higher than those in non-GCB-DLBCL, as compared with TREC values of normal individual in peripheral blood. The mean values of TREC were 0.91 ± 0.15/1000 PBMNCs and (1.22 ± 0.69)/1000 CD3(+) cells in GCB-DLBCL, (0.43 ± 0.29)/1000 PBMNCs and (0.64 ± 0.44)/1000 CD3(+) cells in non-GCB-DLBCL before chemotherapy. TREC values were significantly associated with lower international prognostic index (IPI) grade (r = -0.441, P = 0.015). TREC-level in DLBCL patients was further decreased after chemotherapy, and reached to the lowest level after the 6th cycle of chemotherapy, and during the corresponding period, the mean values of TREC were (0.63 ± 0.34)/1000 PBMNCs and (0.89 ± 0.65)/1000 CD3(+)cells in GCB-DLBCL, (0.19 ± 0.11)/1000 PBMNCs and (0.27 ± 0.25)/1000 CD3(+) cells in non-GCB-DLBCL. TREC-level began to rise obviously 3 months after the last cycle of chemotherapy in most of the DLBCL patients, and came close to normal level in five cases of patients 6 months after the last cycle of chemotherapy.

CONCLUSIONSThymic recent output function was impaired severely in DLBCL patients. There was an important relationship between thymic recent output function before chemotherapy and prognosis, and chemotherapy had influenced the potential of immunological recovery.

Adult ; Aged ; Case-Control Studies ; Female ; Gene Rearrangement, T-Lymphocyte ; Germinal Center ; immunology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; immunology ; pathology ; Male ; Middle Aged ; Receptors, Antigen, T-Cell ; immunology ; Thymus Gland ; immunology ; Young Adult

BACKGROUNDInsulin resistance (IR) is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus. This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.

METHODSA total of 467 consecutive patients undergoing SES-based PCI were divided into IR group (n = 104) and non-IR group (n = 363). The patients were followed up for one year. The rate of major adverse cardiac events (MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test, and the independent risk factors were identified by the Cox regression analysis.

RESULTSMACEs occurred more frequently, and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P < 0.05). IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction (OR = 2.76, 95%CI = 1.35 - 5.47, P = 0.034). Old age, diabetes, and multi-vessel disease were determinants for recurrent angina pectoris after PCI (P < 0.05). Subgroup analysis revealed that IR (OR = 3.35, 95%CI = 1.07 - 13.59, P = 0.013) and multi-vessel disease (OR = 2.19, 95%CI = 1.01 - 5.14, P = 0.044) were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI.

CONCLUSIONSIR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; mortality ; therapy ; Diabetes Mellitus, Type 2 ; complications ; Drug-Eluting Stents ; Female ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Proportional Hazards Models

BACKGROUNDWeight gain following smoking cessation increases cardiovascular risk, but its effects on prognosis after percutaneous coronary intervention (PCI) remain unclear. This study aimed to investigate the relationship between weight gain post smoking cessation and one-year clinical outcome in patients who underwent PCI with drug-eluting stent (DES).

METHODSA total of 895 consecutive male smoking patients were divided into quitters (n = 437) and continuers (n = 458) according to their smoking status after PCI. Weight gain, major adverse cardiac events (MACE, including cardiac deaths, myocardial infarction and revascularization), and recurrent angina were recorded during follow-up for one year.

RESULTSAverage weight gain in quitters was more than that in continuers (1.5 kg vs. -0.03 kg, P < 0.001). Weight was unchanged or increased by more than 1.5 kg in 78.17% of continuers, while 50.57% of quitters had a weight gain of less than 1.5 kg. Compared with continuers, MACE in quitters was significantly reduced after PCI (6.12% vs. 4.81%, P = 0.049), especially recurrent angina (13.97% in continuers vs. 9.84% in quitters, P = 0.027). After adjusting for weight gain and other factors, smoking cessation was independently associated with a lower risk of MACE and recurrent angina (OR = 0.73, P = 0.035). However, weight gain > 1.5 kg (OR = 1.55, P = 0.026) could curtail the benefits from smoking cessation.

CONCLUSIONSWeight gain may reduce the benefits of smoking cessation after PCI with DES implantation. Thus, although smoking cessation is recommended after PCI, weight control should also be highly encouraged for these patients.

Aged ; Angioplasty, Balloon, Coronary ; Drug-Eluting Stents ; Humans ; Middle Aged ; Smoking Cessation ; Weight Gain

OBJECTIVETo evaluate the clinical value of high frequency ultrasound in diagnosing peripheral nerve diseases (PNDs).

METHODSFrom January 2003 to December 2006, 64 cases of PNDs were analyzed retrospectively. The ultrasound diagnosis was compared with the operative and pathological diagnosis.

RESULTSBased on the operative and histopathological results, in 38 patients with trauma or entrapment, 38 among 45 traumatic nerves were rightly diagnosed by ultrasound. The coincidence rate was 84.4%. In 26 patients with original peripheral nerve tumors (PNTs), including 20 neurilemmomas, 4 neurofibromas and 2 malignant neurilemmomas, 16 cases were diagnosed by ultrasound with a coincidence rate of 61.5%. The coincidence rates in limbs and trunk were 86.7% (13/15) and 27.3% (3/11) respectively.

CONCLUSIONSThe study suggests that high frequency ultrasound can locate peripheral nerve trauma precisely, assess the impair degree correctly and provide useful information for clinic diagnosis. The high frequency ultrasound brings better diagnosis outcome in limbs nerve tumors than in trunk.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; Peripheral Nerve Injuries ; Peripheral Nervous System Diseases ; diagnostic imaging ; Retrospective Studies ; Trauma, Nervous System ; diagnostic imaging ; Ultrasonography

BACKGROUNDThe aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model.

METHODSA hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n = 15); splenectomy group (n = 15); CsA group (n = 15); CsA + splenectomy group (n = 15). Levels of IL-2, IFN-gamma, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA + splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenograft after cardiac xenotransplantation.

RESULTSSerum levels of IL-2 and IFN-gamma were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts.

CONCLUSIONSSerum IL-2 and IFN-gamma were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.

Acute Disease ; Animals ; Cricetinae ; Cytokines ; biosynthesis ; Graft Rejection ; prevention & control ; Graft Survival ; Heart Transplantation ; immunology ; Immunohistochemistry ; Mesocricetus ; Rats ; Transplantation, Heterologous ; immunology

This study was aimed to detect the expression of leukemia stem/progenitor cell (LSPC) related genes (ABCB1, BMI-1, HOXB4) in the patients with acute leukemia, and to explore its clinical significance in acute leukemia. Bone marrow samples were collected from de novo acute leukemia patients (41 cases), patients with complete remission (CR, 16 cases) and the patients with non-malignant hematologic diseases (10 cases) respectively. And the expressions of ABCB1, BMI-1, HOXB4 genes were detected by comparative real-time quantitative PCR (RQ-PCR) with SYBR Green assay. The results showed that the expressions of ABCB1, BMI-1, HOXB4 were not detected in the patients with non-malignant hematologic diseases, but were higher (relative expressive level: 4.26 ± 2.26, 3.72 ± 1.91, 3.74 ± 2.38) in de novo acute leukemia patients and lower (relative expressive level: 2.14 ± 1.47, 2.07 ± 0.99, 1.47 ± 0.89) in the acute leukemia patients with CR (p < 0.05). The expressions of LSPC related genes were lower (relative expressive level: 1.77 ± 1.29, 2.09 ± 1.26, 1.78 ± 1.49) in the patients acquired CR/partial remission (PR) than those in the patients not acquired CR/PR (relative expressive level: 7.23 ± 1.78, 3.96 ± 0.92, 4.48 ± 2.57) (p < 0.01). Univariate analysis revealed that there were more cases with the expression of LSPC immunophenotype (CD34(+)CD38(-)CD96(+) and CD34(+)CD38(-)CD123(+)) and more hyperleukocytosis cases in patients with any higher expression of LSPC related gene (p < 0.05). Analysis of multiple parameters discovered larger significance (p < 0.01). It is concluded that there is a good relationship between LSPC related genes (ABCB1, BMI-1, HOXB4) and LSPC immunophenotype. The expression of LSPC-related genes is higher in de novo acute leukemia patients, and lower in patients acquired CR/PR. The patients with higher expressed LSPC-related genes display worse response to chemotherapy, lower CR/PR rate and higher leukocytosis, the analysis of multiple parameters may be a good method for assessing the therapeutic efficacy/prognosis of acute leukemia.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Adolescent ; Adult ; Aged ; Female ; Gene Expression ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; Neoplastic Stem Cells ; metabolism ; Polycomb Repressive Complex 1 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the value of contrast-enhanced ultrasound in the differential diagnosis of solid focal lesions of pancreas (s-FLPs).

METHODSWe retrospectively analyzed the clinical data of 56 s-FLPs examined with contrast agent combined with low mechanical indicators contrast-enhanced ultrasound.

RESULTSThe surrounding pancreas parenchyma enhancement time, lesion enhancement time, and peak enhancement time between different groups of s-FLPs had no significant differences (P > 0.05), while the beginning to peak enhancement time showed significant difference (P < 0.05). When using the enhancement speed as a diagnostic indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 90.5%, 71.4%, and 85.7% for pancreatic carcinoma and 75.0%, 91.7%, and 89.3% for tumor-like pancreatitis. When using the enhancement pattern as a diagnosis indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 85.7%, 78.6%, and 83.9% for pancreatic carcinoma and 75.0%, 100%, and 94.6% for tumor-like pancreatitis. When different indicators were combined, enhancement pattern and enhancement speed showed the best diagnostic results; however, the Youden index was not improved.

CONCLUSIONSDifferent s-FLPs show different enhancement findings on contrast-enhanced ultrasound. The enhancement pattern and enhancement speed are the most useful diagnostic indicators.

Diagnosis, Differential ; Humans ; Pancreas ; diagnostic imaging ; Pancreatic Neoplasms ; diagnostic imaging ; Pancreatitis ; diagnostic imaging ; Retrospective Studies ; Ultrasonography