Autoimmune disease is a condition arisen from an abnormal immune response to the tissue cells itself, its precise mechanism remains unknown, and the failure to distinguish self from non-self is often termed a breach of tolerance and is the basis for autoimmune illness. The tumor necrosis factor-α (TNF-α) induced protein 8 like-2 (TIPE2) is a newly discovered member of TNF-α induced protein 8 (TNFAIP8) family which is an essential negative controller of both innate and adaptive immunity. It has been documented that marked expressions of TIPE2 are evident in various autoimmune diseases, including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), myasthenia gravis (MG) and systemic lupus erythematosus (SLE), which appear to be closely related to the severity, progression as well as prognosis of the illness, thereby contribute to the pathogenesis of autoimmune diseases. Deficient expression of TIPE2 might contribute to the hyper-reactivity of auto-reactive lymphocytes and macrophages, or aggregate inflammatory reaction by prompting high concentration of pro-inflammatory cytokines in peripheral blood, thus, trigger the development and progression of autoimmune diseases. In addition, dysregulation of immune homeostasis could be another latent target involved into the mechanism of autoimmune diseases. The present paper summarized the potential role and its mechanism of TIPE2 in the development of autoimmune diseases.

Aging is a biological process and state characterized by morphological change, hypofunction and metabolic disorder, often accompanied by severe degenerative diseases, including amyotrophy, atherosclerosis, neurodegeneration, and so on. Age-related diseases not only decrease the life quality of the elderly, but also impose great burden on family and society. As population aging, we are increasingly coming to realize that the longevity we want should be healthy aging but not simple increase of lifespan. By researching on the yeast, C. elegans, drosophila, mice and humans, we get to know the mechanisms of aging and methods for anti-aging, such as dietary restriction and use of anti-aging drugs like rapamycin. In this review, we summarized mainly the studies on mechanisms of aging and elaborate associated anti-aging strategies and underlying mechanisms.

Exertional heat stroke (EHS) is an emergency with a high mortality rate, characterized by acute onset and identification difficulties. EHS prevention focuses on evaluating the environment by professionals, making preventive measures in advance, identifying internal and external risk factors for the onset of disease, carrying out prior heat adaptation and endurance training, monitoring the status of high risk persons in real time. After occurrence of EHS, the key to success treatment is on-site accurate identification and diagnosis and rapid implementation of effective cooling measures, thus winning time of EHS patients transferred to the hospital for the treatment. This article reviews the current status of EHS prevention and treatment in domestic and foreign from the scene to the hospital. Summarizing the recognition, diagnosis, cooling measures, treatment concepts and principles of EHS, we hope to provide a reference for the rescue of EHS in hospital and outside.

Objective To explore the effect of topical application of sodium hyaluronate on preventing perivascular adhesion of the vein grafts in rabbits. Methods Thirty-six male New Zealand white rabbits, aged 5 months, were randomly and equally divided into 2 groups: groups A and B. Arterial defect model was established by cutting about 1cm artery from the middle part of the dissected left common carotid artery. A section about 3cm was cut from the right external jugular vein, and the harvested vein was inverted and anastomosed end-to-end to the artery defect. After the anastomosis, the adventitia and two anastomoses of the grafted veins in group A were coated locally with 0.2ml sodium hyaluronate. The grafted veins were obtained 1, 2 and 4 weeks after the operation, with the perivascular adhesion of the vein grafts being examined macroscopically before the resection. HE staining and Masson staining were preformed for histological changes of grafted vein wall and the perivascular adhesion of the vein grafts. At 2, 4 weeks postoperation, the perivascular adhesions of the vein grafts were graded by the grading criteria of adhesion in macroscopic evaluation and histological evaluation. Result At 1, 2 and 4 weeks postoperatively, the macroscopic and histological observation found that the perivascular adhesions in group A were looser than those in group B. The macroscopic grade and histological grade were lower in group A than in group B, there was a significant difference between the two groups at 2 and 4 weeks postoperation (P<0.05). Conclusion Topical application of sodium hyaluronate can reduce the perivascular adhesion and is an ideal treatment strategy for preventing perivascular adhesion of vein grafts.

Objective To investigate the effects of vagus nerve electrostimulation (VNS) on the brain damage of rat middle cerebral artery occlusion (MCAO)/reperfusion model and its mechanism. Methods Twenty four adult male SD rats were randomly divided into two groups (12 each): MCAO/reperfusion group (MCAO group) and MCAO/reperfusion+VNS group (MCAO+VNS group). Subsequently, the neurological function deficit was determined by neurological scoring according to Zea Long scoring method 24h after MCAO/reperfusion. The cerebral infarction volume was determined by TTC assay. The cell apoptosis in brain damage zone was determined by TUNEL assay. Then, the effect of VNS on cAMP response element binding protein (CREB) and p-CREB protein expression was determined by Western blotting. The effect of VNS on Bcl-2 and Bax expression was determined by immunohistochemistry assay. Results Compared with MCAO group, VNS significantly inhibited MCAO-induced neurological deficit (P<0.01), decreased brain infarct volume (P<0.01) and cell apoptosis (P<0.01), increased the expression of p-CREB protein (P<0.01) and the number of Bcl-2-position cells (P<0.01) together with decreasing the number of Bax-position cells (P<0.01). However, VNS did not affect the expression of CREB protein (P>0.05). Conclusion VNS may ameliorate MCAO-induced neurological deficit and decrease brain infarct volume, which may be related to the promotion of p-CREB protein expression level.

Objective To investigate the effect of regulatory dendritic cells treated by extracorporeal photochemotherapy on T cell proliferation. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained and the immature dendritic cells (imDCs) were induced by recombinant human granulocyte and macrophage colony stimulating factors. SPDCs were obtained by PUVA treatment, and ECDCs were co-cultured with imDCs and PUVA-SP to obtain immunoprecipitated dendritic cells. In vitro, imDCs were co-cultured with SPDCs to obtain SPDCs; imDCs were added to 10ng/ml of LPS, and cultured for 1 day to obtain DCs. The expressions of CD11c, CD83 and CD86 on the surface of the cells were detected. The effect of imDCs on the proliferation of recipient T cells was detected by mixed lymphocyte culture method. Results The early apoptosis rate of PUVA-treated cells was 91.33%. The positive expression rates of CD83 and CD86 in ecpDCs were 22.83%±5.26% and 22.06%±4.37%, respectively, which were similar to those of imDCs (15.06%±0.59%, 15.19%±1.83% (P<0.01), but significantly lower than those in DCs (99.79%±0.36%, 99.85%±0.19%, respectively), the difference was statistically significant (P<0.01). The recipient imDC cells phagocyting the appoptotic splenic lymphocytes from the donor significantly inhibited the proliferation of recipient T cells. Conclusion Apoptosis of splenic lymphocytes induced by extracorporeal photochemotherapy can inhibit the maturation of dendritic cells and inhibit the proliferation of T lymphocytes.

Objective To observe the effect of stress on the rapid component of delayed rectifier potassium current (IKr) in rat cardiomyocytes. Methods Forty male SD rats were randomly divided into four groups (10 each): control group (Ctrl), exhaustive group (ES), noise group (WN) and composite group (ES+WN). Stress animal models were prepared as follows: Rats in ES group were undergoing exhaustive swimming as the stress factor, in WN group undergoing white noise and in ES+WN group undergoing exhaustive swimming + white noise as the stress factor. Langendorff device was used to reversely perfuse collagenase for isolating the rat's ventricular myocytes. The effect of stress on IKr current and gating mechanism of single ventricular myocyte was recorded by whole-cell patch clamp technique. Results Compared with the Ctrl group, the tail current density of IKr (IKr,tail) of ventricular myocytes increased significantly in ES group and WN group (P<0.01). The IKr,tail current density of the ventricular myocytes in ES+WN group was significantly higher than that in ES group and WN group (P<0.01), and the effect was voltage dependent. Gating mechanism revealed that the half inactivation voltage of IKr,tail (V1/2,inact) can be shifted to the right in ES group, WN group and ES+WN group when compared with the Ctrl group, and the recovery time constant shortened after inactivation (P<0.01). However, the steady-state activation, fast inactivation constant and voltage dependence of IKr,tail were not statistically significant in ES group, WN group and ES+WN group when compared with the Ctrl group. Conclusion Stress increases the IKr current in rat cardiomyocytes, suggesting it be one of the electrophysiological bases of stress-induced arrhythmia.

Objective To investigate the therapeutic effect of cell penetrating peptide Tat-LK15 mediating small interfering RNA (siRNA) interference with the expression of neuronal nitric oxide synthase (nNOS) in rat spinal dorsal horn on neuropathic pain. Methods The transfection reagent, Tat-LK15, was used to mediate the transfection of rat spinal dorsal horn (SDH) neuronal cells with carboxyfluorescein (FAM), and then the transfection effect was observed under inverted fluorescence microscope. Fifty healthy male SD rats were randomly divided into 5 groups (n=10): control group, sham operation group (sham group), neuropathic pain group (SNL group), Tat-LK15-nNOS siRNA group (TS group) and Tat-LK15-NC siRNA group (TN group). Neuropathic pain was induced by spinal nerve ligation (SNL), rats in control group did not receive operation and only the spinal nerve was exposed in sham group. Groups SNL, TS and TN were made into the models by SNL and implanted intrathecal catheter, intrathecal administration was performed from the 7th day after model establishment, and 10μl normal saline, 10μl TS complex (including 5μg siRNA) and 10μl TN (including 5μg siRNA) were injected intrathecally each day for 7 days. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1 day before (baseline) and 3, 7, 10 and 14 days after model establishment. Then animals were sacrificed on the 14th day after the operation and the lumbar segment (L4-6) of the spinal cord was removed to detect the expressions of nNOS mRNA and protein using q-PCR and Western blotting analysis. Results Tat-LK15 effectively mediated FAM-siRNA into SDH neuronal cells. Compared with sham group, SNL significantly decreased PWMT and PWTL and increased expressions of nNOS mRNA and protein from the 3rd day (P<0.01), but there was no significant difference between the sham and control group. Tat-LK15-nNOS siRNA complex significantly increased PWMT and PWTL and down-regulated nNOS mRNA and protein expressions in TS group compared with SNL group on the days 10 and 14. There was no significant difference between TN and SNL group. Conclusion Tat-LK15 not only can mediate successful nNOS siRNA transfection and inhibit the expression of nNOS, but also effectively relieve SNL-induced neuropathic pain in rats.

Objective To explore the viscoelasticity of relaxed myocardium in vivo through indentation method with an intervention ultrasound indentation system (IUIS). Methods Old myocardial infarction (OMI) models of canine were established by ligating left anterior descending branch of coronary artery for 3 months. The indentation creep tests were used respectively in OMI group and shame group (n=8, each) by IUIS in middle and advanced diastole stage in vivo. Test data were processed with three-parameter solid viscoelasticity model, and the viscoelastic parameters, such as instantaneous elastic modulus (E1), relaxation modulus (E∞), creep elastic modulus (E2) and viscous damping coefficient (η) in normal and infarcted myocardium were obtained and compared. Results All the parameters of E1, E∞, E2 and η increased obviously in OMI group than in sham group shown as follows: 27.81±6.74kPa vs. 6.78±2.43kPa; 17.87±3.59kPa vs. 4.52±1.56kPa; 49.54±14.35kPa vs. 16.82±12.37kPa and 1.97±0.78Pa.s vs. 0.66±0.40Pa.s. The differences were statistically significant (P<0.05). Conclusions IUIS is a feasible method to assess the viscoelasticity of relaxed myocardium in vivo. Three-parameter viscoelasticity model can be used to describe creep properties of relaxed myocardium. Both elastic modulus and viscosity resistance have increased in infarcted myocardium.

Objective To investigate the mechanism of Guiqiyiyuan Ointment (GO) for preventing and treating 12C6+ beam radiation induced lung and kidney bystander effect to provide a new strategy for prevention and treatment of clinical radiation injury. Methods Sixty healthy male Wistar rats were randomly and equally divided into 3 groups: NC group, SR group (simple radiation 2ml/kg), GO group(GO 2ml/kg intragastric administration for 7 days). The right side of the lung was modeled by 12C6+beam radiation. After modeling, the rats were killed at 48h. The left lung, left and right kidney tissues were taken from the rats. The DNA methylation rate was detected by ELISA assay, pathological changes were observed by HE staining, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were detected by immunohistochemistry. Results Compared with the NC group, the level of DNA methylation was decreased significantly (P<0.01), the left lung showed inflammation, no abnormal finding was seen in the left and right kidneys, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly increased in the SR group (P<0.01). Compared with the SR group, the level of DNA methylation was increased significantly (P<0.01), the left lung inflammation became better, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly decreased in the GO group (P<0.01). Dnmt1, Dnmt3a and Dnmt3b proteins were expressed in the cytoplasms of bronchial and renal tubular epithelial cells in all the groups. The NC group presented as light brown-brown staining, showing a weak positive expression, the SR group as brown-brown staining, showing astrong positive expression, and the GO group as light brown-brown staining, showing a moderate positive expression. Conclusion The GO can reduce the bystander effect caused by 12C6+ beam radiation, and its mechanism is related to improving the level of DNA methylation.