BACKGROUND: Experimental autoimmune encephalomyelitis has become the most classical animal model for multiple sclerosis. However, the experimental autoimmune encephalomyelitis model of China presented one-way course of disease. By using proteolipid protein 139-151 and proteolipid protein 178-191, relapse remitting experimental autoimmune encephalomyelitis models may be induced in SJL/J mice which were susceptible to immune, which have similar clinical situation, course and histologicallterations to multiple sclerosis.OBJECTIVE: To establish the relapse remitting experimental autoimmune encephalomyelitis mouse model induced by proteolipid protein, which has similar clinical situation, course and histological alterations to multiple sclerosis.DESIGN: Completely randomized controlled study.SETTING: The centre of Neuro-information, and Neurological Institute,General Hospital of Chinese PLA.MATERIALS: The study was carried out at the Laboratory of Neuro-pathology, General Hospital of Chinese PLA, from February to June 2004.Sixty female SJL/J mice with 8-12 weeks old were selected and randomly divided into proteolipid protein 139-151 group and proteolipid protein-178-191 group with 30 in each.INTERVENTIONS: After injected with proteolipid protein-139-151 or proteolipid protein-178-191, the models of relapse remitting experimental autoimmune encephalomyelitis were induced, and the body weight and neurological signs of each female SJL/J mouse were viewed. The tissue morphological changes of models were observed with hematoxylin and eosin and uxol fast blue stain.MAIN OUTCOME MEASURES: The neurological symptoms and signs,features of relapse and remitting and the perivascular inflammatory cell infiltration, demyelinated lesion of the model of experimental autoimmune encephalomyelitis mouse induced by two proteolipid protein peptides.RESULTS: All 60 mice entered the final analysis. ① Significant neurological symptoms, signs and features of relapse and remitting was manifested in the model of experimental autoimmune encephalomyelitis mouse induced by two proteolipid protein peptides. Obvious phenomena of perivascular inflammatory cuffing, satellitism, predominant perivascular inflammatory cell infiltration and demyelinated lesion were found in spinal and cerebral tissue. ②Changes of body mass: Before immunity, the body mass of mice in two groups was( 17. 84 ± 2.59) g and (17. 88 ± 0.52) g respectively. Onset of relapse of the mice in proteolipid protein-178-191 group was earlier and faster, their body mass had no distinctive change after immunization and the mean body mass was(23.52 ± 2.37) g till the 60th day. Meanwhile, Onset of relapse of the mice in proteolipid protein-139-151 group was later and slower. After the immunity, the body mass of mice was little decrease, and the body mass was (16. 70 ±0.46) g on the 60th day. ③ Neural functional scores: The highest functional scores in the two groups were not different(3.86 ± 1.10vs 3.71 ±1.05, t=0.49, P=0.628).CONCLUSION: The two different antigenic peptides of proteolipid protein can all cause the autoimmune response of central nervous system. Both models have the same characters of relapse and remitting and the severity has no significant difference. But compared with proteolipid protein 139- 151 group,onset and recover of the experimental autoimmune encephalomyelitis of the mice in proteolipid protein 178-191 group were earlier, as well as weight variance was larger, which maybe due to the different structure of two peptides.

Objective:To detect the expression of microRNA-218 (miR-218) in human acute lymphocyte leukemia (ALL) T lymphocytes ( CCRF-CEM) ,explore its effects on the biological features of CCRF-CEM cells and the expression of its target gene c-kit, so as to provide new insights for leukemia treatment.Methods: Using the quantitative real-time polymerase chain reaction ( qRT-PCR) ,we detected the expression of miR-218 in the normal peripheral blood T lymphocytes and CCRF-CEM cells.Forty-eight hours after the miR-218 mimic was transfected into the CCRF-CEM cells,the expression of miR-218 in the CCRF-CEM cells was detected by qRT-PCR.The effect of miR-218 on the CCRF-CEM cell viability was detected using MTT.The effect of miR-218 on the proliferation and apoptosis of CCRF-CEM cell was analyzed using flow cytometry.c-kit gene was identified to be a target gene of miR-218 by luciferase reporter enzyme system,and the effect of miR-218 on the expression of KIT protein in cells were determined using Western blot.Results:As shown by qRT-PCR,compared with that in the normal peripheral blood T lymphocytes,the expressions of miR-218 in ALL T lymphocytes cell lines were significantly decreased ( P<0.01 ) .Compared with the control group, the expression of miR-218 increase significantly in CCRF-CEM cells transfected with miR-218 mimic for 48 hours ( P<0.01).MTT showed that the cell viability decreased significantly after the over-expression of miR-218 in the CCRF-CEM cells ( P<0.05 ) .Flow cytometry showed that the S-phase fraction significantly declined after the over-expression of miR-218 ( P<0.01 ) , and meanwhile the apoptosis of cells also significantly increased (P<0.01).Luciferase reporter gene assay showed that,compared with the control group,the relative luciferase activity significantly declined in the miR-218 mimic transfection group (P<0.01).Compared with the control group,the expression of KIT protein in the CCRF-CEM cells transfected with miR-218 mimic for 48 hours significantly decreased ( P<0.01).Conclusion:The expression of miR-218 decreases in ALL T lymphocytes cell lines.MiR-218 can negatively regulate the expression of KIT protein,inhibit the proliferation and increase the apoptosis of CCRF-CEM cells.Treatment based on the enhanced expression of miR-218 may be a promising strategy for leukemia.

As perimenopausal syndrome is a particularly disturbing condition to the patient, it is practical and necessary to establish a program of comprehensive traditional Chinese medicine therapy for women with perimenopausal syndrome.

Objective To investigate the incidence,distribution patterns,and influencing factors of cerebral microbleed (CMB) in Chinese adult patients with moyamoya disease.Methods Thirty consecutive patients with moyamoya disease confirmed by digital subtraction angiography from the Nanking Stroke Registry Program were included.All patients performed conventional MRI sequences (3.0 T) and susceptibility-weighted imaging.The clinical data,such as medical history,systolic blood pressure,diastolic blood pressure,mean arterial pressure,and white matter lesions were collected.Their fasting blood glucose levels and fibrinogen levels were detected.The numbers of CMB lesion,distribution information,and their relationship with various clinical parameters in patients with moyamoya disease were analyzed.Results Among the 30 subjects included,14 CMBs were detected in 10 patients from 11 hemispheres.The distribution of the lesions was mainly in deep brains (71.4%),especially in the periventricular white matter (50.0%).There was no statistical difference in age,gender,hemorrhage symptoms,blood pressure,white mater lesions,and plasma fibrinogen levels between the CMB positive group and CMB negative group.However,the fasting blood glucose levels in the former was significantly higher than those in the latter (8.0 ± 4.1 mmol/Lvs.4.8 ± 0.4 mmol/L;P =0.035).Multivariate regression analysis showed that the increased fasting blood glucose level was an independent risk factor for the occurrence of CMBs in adult patients with moyamoya disease (OR = 10.992,95% CI 1.325-91.218;P=0.026).Conclusions The CMB lesions are susceptible to Chinese adult patients with moyamoya disease in deep brains,especially in the periventricular white matter.The fasting blood glucose level may influence the incidence of CMBs in patients with moyamoya disease.

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

AIM:To investigate the effect of L-arginine(L-Arg) on expression of bcl-2,bax mRNA during pulmonary ischemia and reperfusion injury(PIRI) in rabbits.METHODS: Single lung ischemia and reperfusion animal model was used in vivo.The rabbits were randomly divided into three groups: sham operated group(sham,n=12),ischemia-reperfusion group(I/R,n=12) and I/R+ L-arginine group(L-Arg,n=12).Changes of several parameters,which included apoptotic index(AI),wet to dry ratio of lung tissue weight(W/D) and index of quantitative assessment of histologic lung injury(IQA),were measured at 300 min after reperfusion in lung tissue.Meanwhile the location and expression of bcl-2,bax mRNA as well as the ratio of bcl-2 mRNA/bax mRNA were observed.The lung tissue was prepared for light microscopic and electron microscopic observation at 60,180 and 300 min after reperfusion.RESULTS: As compared with I/R group,in intima and extima of small pulmonary artery,alveoli,and bronchiole epithelia,the expression of bcl-2 mRNA and the ratio of bcl-2 mRNA/bax mRNA were increased,and the expression of bax mRNA was decreased in L-Arg treatment group.The values of AI,W/D and IQA showed significantly lower than that in I/R group at 180 minutes after reperfusion in lung tissue(P

OBJECTIVETo evaluate the potential repairing effects of low-intensity pulsed ultrasound (LIPUS) irradiation on acute horizontal alveolar bone defects at the mandibular pre-molar areas in Beagle dogs.

METHODSHorizontal alveolar bone defect models were established under enamelo-cemental junction 6 mm at the mandibular third and forth pre-molar buccal regions on both sides in 4 beagle dogs, and bilateral sides of each dog were randomly divided into two groups: Experimental groups with LIPUS irradiation (I(SATA) 30 mW X cm(-2), 20 min x d(-1)) and control groups without opening power source of LIPUS radiation. Dual energy X-ray bone densitometer was used to detect the bony density after an 8 weeks' irradiation. Meanwhile, decalcified bone tissue sections were used to assess the histological effects of new alveolar bone.

RESULTSThe results of new bony density detection in experimental group and control group were (0.6053 +/- 0.0566) g x cm(-2), (0.6047 +/- 0.0552) g x cm(-2), respectively, and there was no statistical significance between the differences of the two groups (P = 0.9839). Hematoxylin-eosin staining of decalcified bone tissue sections demonstrated that there were more osteoblasts lining at the edge of new alveolar bone in the experimental groups than that scattered in the control groups, and Masson staining revealed that collagens in new alveolar bone stained bright red indicating higher maturity in the experimental groups, while in the control groups mainly stained blue with some virescent areas indicating lower maturity.

CONCLUSIONLIPUS irradiation on acute horizontal alveolar bone defects has potential repairing effects.

Animals ; Bone and Bones ; Dogs ; Osteoblasts

Objective To investigate the effects of functional magnetic resonance imaging (fMRI)with acute ischemic stroke (AIS) patients,and to evaluate the relationship between brain reorganization and motor recovery.Methods Nine AIS patients and 9 healthy volunteers were assessed by fMR1 during passive finger clenching at a pace of 1 Hz.The fMRI results were analyzed using SPM2 software.Lateral indices (LIs) and activated regions were calculated,and the relationship between LI and muscle strength was examined.Results In the control group,activation was observed in the contralateral sensorimotor cortex (SMC) and the bilateral supplementary area (SMA) during the passive movement.In the AIS group,similar results were recorded dur- ing unaffected hand movement,but the ipsilateral activation areas were greater than those on the eontralateral side during movement of the affected hand.LI results confirmed that movement of the affected hand mainly elici- ted activation in the ipsilateral hemisphere.Conclusion The different fMRI manifestations of patients and nor- mal subjects reflect brain compensation,and fMRI is valuable for studying the correlation between motor function and brain reorganization.

Objective: To investigate the multidetector computed tomography (MDCT) features of fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) with germline or somatic mutations, and compare them with those of papillary type II RCC (pRCC type II). Materials and Methods: A total of 24 patients (mean ± standard deviation, 40.4 ± 14.7 years) with pathologically confirmed FH-deficient RCC (15 with germline and 9 with somatic mutations) and 54 patients (58.6 ± 12.6 years) with pRCC type II were enrolled. The MDCT features were retrospectively reviewed and compared between the two entities and mutation subgroups, and were correlated with the clinicopathological findings. Results: All the lesions were unilateral and single. Compared with pRCC type II, FH-deficient RCC was more prevalent among younger patients (40.4 ± 14.7 vs. 58.6 ± 12.6, p < 0.001) and tended to be larger (8.1 ± 4.1 vs. 5.4 ± 3.2, p = 0.002). Cystic solid patterns were more common in FH-deficient RCC (20/24 vs. 16/54, p < 0.001), with 16 of the 20 (80.0%) cystic solid tumors having showed typical polycystic and thin smooth walls and/or septa, with an eccentric solid component. Lymph node (16/24 vs. 16/54, p = 0.003) and distant (11/24 vs. 3/54, p < 0.001) metastases were more frequent in FH-deficient RCC. FHdeficient RCC and pRCC type II showed similar attenuation in the unenhanced phase. The attenuation in the corticomedullary phase (CMP) (76.3% ± 25.0% vs. 60.2 ± 23.6, p = 0.008) and nephrographic phase (NP) (87.7 ± 20.5, vs. 71.2 ± 23.9, p = 0.004), absolute enhancement in CMP (39.0 ± 24.8 vs. 27.1 ± 22.7, p = 0.001) and NP (50.5 ± 20.5 vs. 38.2 ± 21.9, p = 0.001), and relative enhancement ratio to the renal cortex in CMP (0.35 ± 0.26 vs. 0.24 ± 0.19, p = 0.001) and NP (0.43 ± 0.24 vs. 0.29 ± 0.19, p < 0.001) were significantly higher in FH-deficient RCC. No significant difference was found between the FH germline and somatic mutation subgroups in any of the parameters. Conclusion The MDCT features of FH-deficient RCC were different from those of pRCC type II, whereas there was no statistical difference between the germline and somatic mutation subgroups. A kidney mass with a cystic solid pattern and metastatic tendency, especially in young patients, should be considered for FH-deficient RCC.

OBJECTIVETo investigate the effect of wortmannin on endothelial cells proliferation and migration induced by high glucose Müller cell conditioned medium (HGMCM).

METHODSImmunofluorescence, flow cytometry and Boyden chamber migration models were used to analyze the effect of wortmannin on endothelial cells.

RESULTS50 nmol/L wortmannin could significantly inhibit the proliferation and migration of endothelial cells induced by HGMCM. The percentage of endothelial cells in S phase was obviously decreased [from (37.82 +/- 0.57)% to (21.91 +/- 0.23)%, P < 0.01], while there was an increase in the percentage of cells in G(0)/G(1) phase [from (54.57 +/- 1.19)% to (65.59 +/- 0.41)%, < 0.01] and G(2)/M phase (< 0.05).

CONCLUSIONWortmannin can inhibit proliferation and migration of endothelial cells induced by HGMCM, suggesting that wortmannin carries an anti-angiogenetic ability in diseased retina.

Androstadienes ; pharmacology ; Animals ; Cell Cycle ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media, Conditioned ; pharmacology ; Endothelial Cells ; cytology ; Female ; Glucose ; Humans ; Male ; Neovascularization, Pathologic ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; Rabbits ; Retina ; cytology