10.3969/j.issn.1000-3606.2013.06.013

The nuclear factor erythroid 2 related factor 2 (Nrf2) is a key protein of endogenous antioxidant defense systems in the body. In response to oxidative stress, Nrf2 translocates to nucleus and binds to antioxidant response elements (ARE), regulating the expression of a large amounts of antioxidant genes and maintaining a proper redox balance. The pathological processes of neurodegenerative diseases are associated with generation of reactive oxygen species, which cause oxidative stress. Oxidative stress plays a cardinal role in the onset and progression of neurodegenerative diseases. Nrf2-inducer compounds can reduce oxidant stress and have shown therapeutic efficacy in many neurodegenerative disease models. How to activate the Nrf2 signaling pathway effectively has been received much attention. Here we provided an overview of specific mechanism of Nrf2-ARE pathway and the protective effects of Nrf2 in different neurodegenerative diseases, and summarized the Nrf2 activators recently in preclinical study.

BACKGROUND:Matrix metaloproteinases are now generaly considered to be able to degrade al extracelular matrices. Hypersecretion of matrix metaloproteinases or reduction in tissue inhibitors of matrix metaloproteinases leads to destruction of the dynamic balance of extracelular matrix. OBJECTIVE: To elucidate the role of matrix metaloproteinase-1 and tissue inhibitor of matrix metaloproteinase-1 in the pathogenesis and progression of intervertebral disc degeneration. METHODS:A total of 60 patients with intervertebral disc degeneration were included. Mild, moderate, and severe degeneration signals appeared on MRI imaging of the patients. Meanwhile, 20 patients with vertebral fracture, mainly cervical spine fracture, were selected as the control group. Venous blood samples were colected before the surgery; the intervertebral disc specimens were sequentialy colected. RESULTS AND CONCLUSION: Serum and tissue levels of matrix metaloproteinase-1 in patients with intervertebral disc degeneration were significantly increased compared with the control group (P < 0.05), and furthermore those were significantly increased in patients with severe disc degeneration compared with patients with mild and moderate disc degeneration (P < 0.05). However, serum and tissue levels of tissue inhibitors of matrix metaloproteinases did not differ significantly between the disc degeneration and control groups (P > 0.05). These results indicate that hypersecretion of matrix metaloproteinase-1 occurs in patients with intervertebral disc degeneration; however, the expression of tissue inhibitor of matrix metaloproteinase-1 is not correlated with intervertebral disc degeneration.

Objective To identify the arteriographic manifestations of emergency uterine artery angiography and the efficacy of embolization treatment of postcesarean massive hemorrhage caused by placenta previa.Methods Emergency uterine artery angiogra-phy was performed in 35 patients with massive hemorrhage after cesarean section due to placenta previa.Emergency uterine arterial embolization (EUAE)was conducted using embolic agents such as tricacryl gelatin microsphere (TAGM)and gelatin sponge.Arte-riographic manifestations and effect of the emolotherapy were analyzed retrospectively.Results Contrast extravasations were con-firmed in 27 patients,and uterine artery pseudoaneurysms were in 8.The hemorrhage completely stopped after embolotherapy in all patients.A 12 month follow-up showed no recurrence hemorrhage and any severe complications were observed in all patients,such as necrosis of the uterus and ovary.Conclusion EUAE can be used as a safe,effective and minimally invasive therapeutic option for postcesarean massive hemorrhage caused by placenta previa.It is the key for the success of embolotherapy to choice and use reasona-ble embolic agents.

Objective To investigate the causes of coma children in Pediatric Intensive Care Unit (PICU).Methods The causes of 210 children with coma were retrospectively analyzed.Results Among 210 cases,150 cases attributed to medical disease (71.43 ％),while 60 cases attributed to surgical disease (28.57 ％).110 cases were caused by infection(52.38％),58 cases were caused by cranioeerebral trauma (27.62％),while 31 cases involved in traffic accident(14.76％).Conclusion The main cause of coma in PICU is infectious diseases,but traffic accident trauma coma has been increased.It is positive to correct treatment and improve prognosis to recognize the cause as soon as possible.

ObjectiveTo investigate the role of apoptosis played in myocardial hypertrophy and the effect of L-arginine (L-Arg) on the pathogenesis.Methods36 rats were randomly divided into the control group, model group and L-Arg treating group. The animal model of over-loading myocardial hypertrophy was made, and systolic blood pressure (SBP)and the cardiac indexes were measured, spectrophotography and flow cytometry were used to detect the content of nitric oxide (NO), activity of superoxide dismutase (SOD) and apoptosis rate.ResultsIn the model group, SBP, cardiac indexes and myocardial apoptosis rate increased, the content of NO and activity of SOD decreased compared with the control group. While, in the L-Arg treating group, SBP, cardiac indexes and apoptosis rate decreased, the content of NO and the activity of SOD increased compared with the model group.ConclusionMyocardial apoptosis may play an important role in the pathogenesis of myocardial hypertrophy and cause the losing of myocardial cells. L-Arg induces the increasing production of NO and inhibits myocardial apoptosis through increasing the activity of SOD.

Objective To study the role of psychological factors in the onset of psoriasis,to investigate the role of monoamine substances in the course of psychological factors-associated psoriasis,and to reveal the psychoneurologic pathogenesis of psoriasis.Methods The psychological factors were assessed with life events scale and questionnaire of A character.The serum levels of norepinephrine(NE),dopamine(DA)and5-hydroxyindoleacetic acid(5-HIAA)were detected with high-performance liquid chromatography(HPLC).Results It was shown that there was an overall tendency of weak A character and moderate depression and anxiety in psoriasis patients.The concentrations of NE,DA and5-HIAA were higher in psoriatic patients than those in normal controls(P

BACKGROUND:Cervical decompression and fusion internal fixation wil accelerate adjacent segment disc degeneration, and it is not clear whether single segment instaibility can increase the adjacent segment disc degeneration. OBJECTIVE:To study the changes of morphology, proteoglycan and col agen type Ⅱ in the adjacent intervertebral disc of the cervical instability models. METHODS:Sixteen New Zealand white rabbits were divided into two groups randomly, with eight rabbits in the control group and eight rabbits in the model group. The animal cervical instability models were made by destroyed partly annulus fibrosus and absorbed C 5/6 nucleus pulposus through anterior cervical puncture. After 12 weeks, the animal models were tested by X-ray film. Al rabbits were sacrificed and 10 mg nucleus pulposus of the intervertebral discs of C 4/5 cut from sagittal plane were harvested and stored under 0 ℃. The content of proteoglycan in nucleus pulposus was tested with phloroglucinol method. Then, the paraffin sections of intervertebral disc tissues were taken for hematoxylin-eosin staining and SABC immunohistochemical staining. RESULTS AND CONCLUSION:The notochord cells of C4/5 intervertebral discs in the experimental group was decreased, and being replaced by fibroblast-like cells. Round chondrocytes could be seen occasional y and intervertebral discs annulus fibrosus became rough and arranged disorderly, the hyaline degeneration and pigmentation were observed as wel as the fibrochondrocytes, and there was a gap between inner and outer annulus fibrosus. The content of proteoglycan was decreased in the nucleus pulposus, and there was significant difference between two groups. The col agen type Ⅱ in the degenerative disc nucleus pulposus and annulus fibrosus of the experimental group was lower than that of the control group. Cervical instability can lead to adjacent intervertebral disc degeneration with the morphological changes and decreased content of proteoglycan and col agen type Ⅱ.

Objective To explore the effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on memory CD4+T cells of focal proliferative IgA nephropathy (IgAN)patients.Methods (1) Total of twenty incipient focal proliferative IgAN patients (Lee classification:Ⅲ level) were chosen as IgAN group and 20 healthy volunteers were chosen as healthy control group.The level of serum 1,25(OH)2D3 was measured by radioimmunoassay (RIA).Peripheral blood mononuclear cells (PBMCs) were separated by the method of Ficoll density gradient centrifugation and were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25(OH)2D3,Dexamethasone(DEX) and 1,25(OH)2D3and DEX combined.PBMCs were cultured for 72 hours and the levels of IFN-γ,IL-4,IL-17A,Foxp3 were measured by flow cytometry(FCM),standing for the levels of Th1,Th2,Th17,Treg.(2) IgAN group was divided into two subgroups (proteinuria ＜ 1 g/24 h subgroup,proteinuria≥ 1 g/24 h subgroup),then the serum levels of 1,25(OH)2D3,IFN-γ,IL-4,IL-17A,Foxp3 were compared.Results Compared with healthy control group,serum 1,25(OH)2D3 level of IgAN group was significantly lower (P ＜ 0.05).Serum 1,25(OH)2D3 level in proteinuria≥ 1 g/24 h subgroup was significantly lower than proteinuria ＜ 1 g/24 h subgroup and healthy control group (P ＜ 0.05).The level in proteinuria ＜ 1 g/24 h subgroup was lower than healthy control group,but the difference was not statistically significant (P ＞ 0.05).(2) The levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4,IL-17A/Foxp3 in IgAN group increased significantly compared with healthy control group (all P ＜ 0.05),and the level of Foxp3 decreased significantly (P ＜ 0.05).The level of IL-4 also increased,but the difference was not statistically significant (P ＞ 0.05).The levels of IFN-γand IL-17A and the ratio of IL-17A/Foxp3 in proteinuria≥ 1 g/24 h subgroup increased significantly,and the level of Foxp3 decreased significantly,compared with urinary protein ＜ 1 g/24 h subgroup and healthy control group (P ＜ 0.05).The ratio of IFN-γ/IL-4 in proteinuria≥1 g/24 h subgroup and proteinuria ＜ 1 g/24 h subgroup all increased,compared with healthy control group,and the ratio in proteinuria≥ 1 g/24 h subgroup increased significantly (P ＜ 0.05).There was no significant difference in the level of IL-4 among all groups.(3) After treatment with 1,25(OH)2D3,the levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3 decreased significantly,and the level of Foxp3 increased significantly (P ＜ 0.05),and these effects were more obvious as the increase of the drug concentration.The level of IL-4 did not change significantly.The combination of 1,25(OH)2D3 and DEX had a synergistic inhibition on the production of IFN-γ,IL-4,IL-17A,and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3,and had a synergistic promotion on the production of Foxp3.Conclusions There is a certain extent of vitamin D deficiency in focal proliferative IgAN patients,which may be associated with the severity of proteinuria.The disorder of immunomodulatory effects of memory CD4+ T cell might exist in the patients of focal proliferative IgAN.1α,25-dihydroxyvitamin D3 might have beneficial effects on the immunoregulation of memory CD4+T cells of focal proliferative IgAN patients.

BACKGROUND:Destroying posterior stable structure of cervical vertebra may facilitate the ligamentum flavum regeneration. Whether anterior cervical instability can induce the regeneration in posterior and adjacent ligamentum flavum remains unclear.
OBJECTIVE:To observe the changes of transforming growth factor-β1 expression and histopathology in the ligamentum flavum of cervical instability animal models.
METHODS:Thirty-six New Zealand white rabbits were randomly divided into control group and experimental group, with 18 rabbits in each group. In the experimental group, cervical instability animal models were established made through destroying annulus fibrosus by anterior puncture and absorbing nucleus pulposus in C4/5 . And no intervention was given to the control group.
RESULTS AND CONCLUSION:Compared with the control group, fibers in the C 3/4, 4/5, 5/6 ligamentum flavum arranged disorderly and the glass like degeneration was found in the experimental group. The expression of transforming growth factor-β1 in ligamentum flavum was increased, especial y in C 4/5 , in the experimental group. At 4, 8, 12 weeks, transforming growth factor-β1 expression in the C 3/4, 4/5, 5/6 ligamentum flavum segments was similar between the two groups. Experimental findings indicate that, anterior cervical instability can induce the regeneration in posterior ligamentum flavum, especial y in the injured segment.