Background Optic neuropathy is one of the diabetic eye complications.Rosiglitazone,a peroxisome proliferator activated receptor γ(PPARγ) agonist,plays a very important role in arresting the pathogenesis and development of diabetes.However,the role of PPARγ in diabetic optic neuropathy is unclear.Objective This study was to investigate the protective effect of rosiglitazone against diabetic optic neuropathy and its mechanism.Methods Male Sprague-Dawley rats were randomly divided into the control group,diabetic group and rosiglitazone group,with 10 rats for each group.Diabetic models were induced by injecting 50 mg/kg of streptozotocin via the caudal vein,and rosiglitazone(5 ng/[kg· d])was used in the rats of the rosiglitazone group by intragastric administration every day for four weeks.At the end of the experiment,the fasting blood sugar(FBS) was tested in all the animals.The level of vascular endothelial growth factor(VEGF) in the blood plasma was detected by ELISA.Optical neural tissues were obtained from the rats of each group,and Lauck fast Blue myelin stain was used to examine the morphology of the optical myelin.The expression of neural cell adhesion molecule (NCAM) mRNA and protein in the optic nerve was detected by real time PCR and Western blot,respectively.Results The levels of FBS,blood plasma VEGF,NCAM mRNA and protein in the optic nerve were significantly different among the control group,diabetic model group and the rosiglitazone group after the administration of 5 nmg/(kg · d) rosiglitazone for 4 weeks (F =6.12,P＜0.01 ; F =5.14,P＜0.05 ; F =4.75,P＜0.05 ; F =4.87,P＜0.05).Compared with the control group,the level of FBS significantly increased in the diabetic model group(t =2.26,P＜O.05),and that in the rosiglitazone group significantly declined in comparison with the diabetic model group(t=2.08,P＜0.05).The optic nerve exhibited a normal morphology in the control group as revealed by the Lauck fast Blue myelin staining;however,severe demyelination of the optic nerve and proliferation of glial cells were found in the diabetic model group,and mild demyelination of the optic nerve and proliferation of glial cells were seen in the rosiglitazone group.Blood plasma VEGF was(28.76±4.21)ng/L in the control group and(134.28±11.36)ng/L in the diabetic model group,showing a significant difference between them (t=2.36,P ＜ 0.05).Compared with the model group,the blood plasma VEGF was significantly lower in the rosiglitazone group ([42.67 ± 5.83] ng/L) than that in the diabetic model group (t =2.17,P＜ 0.05).Expression of NCAM mRNA and protein in the optic nerve significantly decreased in the diabetic model group compared with the control group(t =2.21,t =2.58,both at P＜0.05);while those in the rosiglitazone group were significantly elevated in comparison with the diabetic model group(t =2.19,t =2.67,both at P＜O.05).Conclusions Rosiglitazone can protect optic nerve from damage in diabetic rats mainly by downregulating blood plasma VEGF level and upregulating NCAM expression.

OBJECTIVETo establish and characterize imatinib-resistant gastrointestinal stromal tumor (GIST) xenografts. Further provided an ideal experimental platform through the imatinib-resistant GIST xenografts to investigate the mechanism of resistance to imatinib.

METHODSImatinib-resistant GIST cells were injected under the skin of athymic nude mice to establish animal models of human imatinib-resistant GIST. The molecular and histopathologic features of GIST xenografts were also analysed and compared with their counterpart of cell lines.

RESULTSThe xenograft tumor models had been established by subcutaneously injection of GIST cells into nude mice. Immunohistochemistry results showed CD117 expression was positive in GIST-PR2 xenograft tumor, but negative in GIST-R. In GIST-PR1, tumor areas showing rhabdomyoblastic differentiation were presented next to areas with classic GIST morphology. The rhabdomyoblastic component demonstrated consistently positivity for desmin and myogenin, whereas CD117 was completely negative. The mutation profiles of these xenograft tumors were the same as their counterpart of cell lines.

CONCLUSIONSHuman GIST xenografts with mutation in c-kit have been established from imatinib-resistant GIST lines. Those models will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.

Animals ; Antineoplastic Agents ; pharmacology ; Benzamides ; Cell Differentiation ; Cell Line, Tumor ; Desmin ; metabolism ; Drug Resistance, Neoplasm ; Female ; Gastrointestinal Neoplasms ; genetics ; metabolism ; pathology ; Gastrointestinal Stromal Tumors ; genetics ; metabolism ; pathology ; Humans ; Imatinib Mesylate ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mutation ; Myogenin ; metabolism ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Pyrimidines ; pharmacology ; Rhabdomyosarcoma ; metabolism ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo compare the effect and safety of Shang Ring circumcision with those of conventional circumcision in the treatment of redundant prepuce or phimosis.

METHODSWe retrieved the randomized controlled trials on Shang Ring circumcision and conventional circumcision for the treatment of redundant prepuce or phimosis published at home and abroad. Relevant data were selected according to the Cochrane Handbook for Systematic Reviews by two reviewers after quality evaluation of the included trials, and the statistical software RevMan 5.0 was used for meta analysis.

RESULTSTotally 8 randomized controlled trials with 2277 cases were included in this study. Compared with conventional circumcision, Shang Ring circumcision showed a shorter operation time (SMD = -5.82, 95% CI [ -7.39, -4.24], P<0.00001), less intraoperative blood loss (SMD = -3.28, 95% CI [ -3.47, -3.09], P<0.00001), lower rate of infection (OR = 0.44, 95% CI [0.26, 0.72], P=0.001), lower rate of postoperative bleeding (OR =0.05, 95% CI [0.02, 0.12], P<0.00001), higher rate of satisfaction with the postoperative penile appearance (OR=12.72, 95% CI [1.30, 124.56], P=0.03), lower intraoperative pain score (SMD = -3.32, 95% CI [ -3.50, -3.14], P<0.00001), and lower 24-hour-postoperative pain score (SMD = -3.28, 95% CI [ - 3.47, - 3.00], P<0.00001), but longer wound healing time (OR=1.46, 95% CI [1.03, 1.90], P<0.00001).

CONCLUSIONIn comparison with conventional circumcision, Shang Ring circumcision has the advantages of shorter operation time, fewer complications, mild pain, and higher rate of satisfaction with the postoperative penile appearance. However, more high-quality randomized controlled trials with large samples are required to lend further support to our findings.

Circumcision, Male ; methods ; Humans ; Male ; Phimosis ; surgery ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVETo study the clinical and laboratory characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV.

METHODSThe clinical data of 13 children with CAEBV, as well as 15 cases of acute EBV infection (AEBV) as controls, were analyzed, including clinical manifestations, EBV antibodies, EBV DNA, and peripheral blood lymphocyte subsets.

RESULTSBoth groups of patients had infectious mononucleosis-like symptoms such as fever, hepatomegaly, splenomegaly, and lymphadenectasis, but CAEBV patients had a longer course of disease and continuous and recurrent symptoms. Compared with the AEBV group, the CAEBV group had a significantly higher EBV DNA load in peripheral blood (P<0.05), a significantly higher VCA-IgG titer (P<0.05), and significantly lower numbers of white blood cells, lymphocytes, B cells, total T cells, CD4+ T cells, and CD8+ T cells in peripheral blood (P<0.05). Among 13 CAEBV patients followed up, 8 cases died, 2 cases showed an improvement, 2 cases had a recurrence, and 1 case was lost to follow-up after being transferred to another hospital. All the AEBV patients were cured and had no recurrence during the one-year follow-up.

CONCLUSIONSThe clinical manifestations of CAEBV vary in children. It is difficult to distinguish CAEBV from AEBV early. More attention should be paid to CAEBV because of its severe complications, poor prognosis, and high mortality. Measurement of EBV DNA load, VCA-IgG titer, and lymphocyte subsets in peripheral blood may be helpful in the diagnosis and differential diagnosis of CAEBV.

Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Epstein-Barr Virus Infections ; diagnosis ; immunology ; virology ; Female ; Humans ; Infant ; Lymphocyte Subsets ; immunology ; Male

A disintegrin-metalloproteinase 28 (ADAM28) is one of important members of ADAM family, that is involved in various biological events including cell adhesion, proteolysis, growth and metastasis of solid tumors and hematological malignancies. Studies have shown that ADAM28 is highly expressed in several human tumors, such as lung, breast and bladder cancers, and chronic lymphocytic leukemia, and its tissue expression levels correlate with cancer metastasis. ADAM28-mediated cancer cell metastasis may be related with the cleavage of von Willebrand's factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3) and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P-selectin-mediated cell adhesion. This review summarizes the basic and translational aspects of ADAM28 biology that might stimulate the interest in ADAM28 research and discovery of novel ADAM28 targets, providing potential novel therapies for metastatic cancers.
ADAM Proteins ; metabolism ; Cell Adhesion ; Connective Tissue Growth Factor ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; metabolism ; Neoplasm Metastasis ; Neoplasms ; pathology ; von Willebrand Factor ; metabolism

OBJECTIVETo illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.

METHODThe BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.

RESULTThe primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.

CONCLUSIONThe significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Sensitivity and Specificity ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tumor Necrosis Factor-alpha ; blood

This study was purposed to investigate the mechanism of thrombocytopenia in patients with systemic lupus erythematosus (SLE) through detecting anti-megakaryocyte antibodies in SLE patients. The serum anti-megakaryocyte antibodies in 36 SLE cases with thrombocytopenia were detected by using indirect immunofluorescence, the detected results were compared with detected results of 30 SLE cases without thrombocytopenia and 30 healthy persons. The results showed that the positive incidences of anti-megakaryocyte antibody in serum of 36 SLE cases with thrombocytopenia, 30 SLE cases without thrombocytopenia and 30 healthy persons were 19.4% (7/36), 6.7% (2/30) and 3.3% (1/30) respectively. As compared with SLE patients without thrombocytopenia and healthy persons, SLE patients with thrombocytopenia had higher incidence of anti-megakaryocyte antibodies, moreover there was significant difference between SLE patients with thrombocytopenia and healthy persons (p < 0.05), while there was no significant difference between SLE patients with or without thrombocytopenia (p > 0.05). It is concluded that autoantibodies against megakaryocytes exist in SLE patients and may partially contribute to the incidence of thrombocytopenia in SLE patients. The detection of anti-megakaryocyte antibodies with a enough case number is needed to make a final conclusion on thrombocytopenia pathogenesis in SLE.
Adult ; Autoantibodies ; blood ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Lupus Erythematosus, Systemic ; blood ; immunology ; Male ; Megakaryocytes ; immunology ; Middle Aged

BACKGROUNDDecoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2.

METHODSHepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant.

RESULTSDcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05).

CONCLUSIONSLoss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.

Analysis of Variance ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; genetics ; physiology ; Hep G2 Cells ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Tumor Necrosis Factor, Member 6b ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Relevant research in recent years has demonstrated that the atrial fibrillation occurrence rate is significantly higher in patients with cirrhosis. The most common indication for long-term anticoagulant therapy is chronic atrial fibrillation. The use of anticoagulant therapy greatly reduces the incidence rate of ischemic stroke. Patients with cirrhosis combined with atrial fibrillation have an elevated risk of bleeding and embolism during anticoagulant therapy due to cirrhotic coagulopathy. At the same time, the liver of such patients will go through varying levels of metabolism and elimination while consuming currently approved anticoagulant drugs, thereby increasing the complexity of anticoagulant therapy. This article summarizes the clinical studies on the risks and benefits of anticoagulant therapy in order to provide a reference for patients with cirrhosis combined with atrial fibrillation.
Humans ; Atrial Fibrillation/epidemiology* ; Stroke/epidemiology* ; Anticoagulants/therapeutic use* ; Hemorrhage ; Liver Cirrhosis/drug therapy* ; Risk Factors