BACKGROUND:Microtubule-associated protein-2 is a kind of important regulatory factor in regulating tubulin assembly. As one of the main members of microtubule-associated proteins, microtubule-associated protein-2 plays an important role in the repairing and development of the nervous system function. It has been found that microtubule-associated protein-2 can promote the repair and rebuilding of injured nerves. OBJECTIVE:To summarize the relationship between microtubule-associated protein-2 and nerve injury as wel as the mechanism of action. METHODS:The PubMed database and CNKI database were retrieved by the fist author for the articles related to microtubule-associated protein-2 published from January 1976 to January 2015. The key words were“microtubule-associated protein-2 (MAP-2), nerve injury, progress”in English and Chinese, respectively. In the same field, articles published recently or in authorized journals were preferred. Repetitive or old articles were excluded, and final y 82 articles were included in result analysis. RESULTS AND CONCLUSION:Microtubule-associated protein-2 is involved in nerve repair, and plays a promoting role in neuronal morphology and plasticity. To increase the concentration of microtubule-associated protein-2 contributes to the recovery of neurologic function in the early stage after nerve injury.

AIM: To explore the mechanism of myocardium protection after ischemia/reperfusion (I/R) injury by preconditioning with ischemia in human. METHODS: Thirty - six patients underwent valve replacement were divided into ischemic preconditioning group (IP group, 20 cases) and non -ischemic preconditioning group (control group, 16 cases) according to whether they were given single cycle reperfusion before cardioplegia or not. Serum levels of interleukin -8 and 10 were measured with ELISA. Expressions of myocardial Bel -2 and caspase -3 were analyzed. RESULTS: The inflammatory factors IL - 8 and IL - 10 increased to the highest level in serum at 6 h after declamping and recovered to normal level on 5 d after declamping. On 6 h, 1 d and 2 d after declamping, serum level of IL -8 was significantly lower in IP group than that in control group ( P < 0.05 ) , but serum level of IL -10 was higher in IP group (P < 0.05 ). Expression of myocardial Bel - 2 and caspase - 3 increased in both groups after reperfusion, and Bel - 2 was lower in the control group than that in IP group while the level of caspase - 3 was higher (P < 0.05). Expression of myocardial Bel - 2 had positive correlation with IL - 10 and negative correlation with IL - 8.CONCLUSION: Ischemic preconditioning has the effect of protection of human myocardial cells after ischemia/reperfusion injury through decreasing systemic inflammatory response following ischemia reperfusion injury.

Objective Both underuse and overuse of anticoagulant therapy may lead to severe adverse effects. Emerging portable monitering devices, which provides reliable and accurate measurements, were reported to be potential alternatives to tra-ditional monitering recta-analysis regimens. This study was intended to evaluate the effects of serf-monitoring or serf-management (self-testing and serf-dosing) of anticoagulant as compared with that of traditional monitoring. Methods Relevant trials reported before October 2008 were identified in a number of electronic database and analyzed with software RevMan 4.2. The primary out-comes included death from any cause, major bleeding event, thromboembolic event and the proportion of patients whose interna-tional normalized ratio (INR) were within the therapeutic range. Results Seventeen RCT of serf-monitoring were identified.Pooled estimates revealed significant reductions in the thromboembolic events (odds ratio 0.46, 95% CI0.33 -0.64), all-cause mortality (0.61,0.40 -0.93), and major haemorrhage (0.80, 0.58 - 1.10) with self-monitoring as comparing with traditional monitoring. No difference was noted in minor haemorrhage. 15 trials reported improvements in the mean proportion of patients whose INR were within target range. Conclusion Self-management regimen is superior to traditional monitoring in the outcomes of oral anticoagulation. Patients capable of self-monitoring and serf-adjusting have fewer thromboembolic events and lower mortali-ty than those undergoing self-monitoring alone. However, self-monitoring requires education and training for patients.

Objective To explore the expression of TLR4/NF-κB pathway in cerebral injury resulting from DHCA ( deep hypothermia circulatory arrest ) as well as the effect of SACP ( selective antegrade cerebral perfusion). Methods Twelve pigs were randomly assigned to DHCA group (n = 6) or SACP group (n = 6) at 18 ℃ for 80 min. IL-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 was determined through qRT-PCR and Western blot. Results Serum IL-6 level of SACP group was significantly lower at the end of circulation arrest and experiment and apoptotic index and NF-κB protein were apparently lower in SACP group (P < 0.05). The level of TLR4 protein and mRNA from SACP group decreased significantly (P < 0.05). Conclusions TLR4/NF-κB pathway plays a critical role in pathogenesis of DHCA cerebral injury and attenuating TLR4/NF-κB cytokines probably contributes to neuroprotection of SACP. TLR4/NF-κB pathway may be a novel target for DHCA.

AIM:To observe the expression of hypoxia-inducible factor 1 (HIF-1) and neuroglobin (NGB) in piglet cortex during deep hypothermic circulatory arrest.METHODS:Wuzhishan piglets were randomly assigned to car-diopulmonary bypass group ( CPB group) , 40 min of circulatory arrest ( CA) at 18 ℃ without cerebral perfusion ( DHCA group) or with selective antegrade cerebral perfusion ( SACP group) .After 180 min of reperfusion, cortical tissue was har-vested for determining HIF-1αand NGB expression by HE staining, Western blot and real-time PCR.RESULTS:Severer cerebral injury was observed in DHCA group than that in SACP group.After 180 min of reperfusion, HIF-1αprotein and mRNA levels were significantly higher in DHCA group than those in CPB group (P<0.05).Accordingly, SACP animal had higher levels of HIF-1αprotein and mRNA than those in DHCA group (P<0.05).Simultaneously, higher NGB pro-tein and mRNA levels were found in DHCA group than those in CPB group after 180 min of reperfusion ( P<0.05) .The SACP animal had higher levels of NGB protein and mRNA than those in DHCA group (P<0.05).CONCLUSION:Up-regulation of HIF-1 and NGB are involved in the mechanism against cerebral injury resulting from DHCA in the cortex and possibly a part of cerebral protective effect of SACP.

Objective To evaluate the miRNA change between hypothermia circulatory arrest at different temperature and its impact on intestinal protection.Methods Sixteen piglets were randomly(n =4) divided into four groups:deep hypothermia circulatory arrest (DHCA,18℃) group,moderate hypothermia circulatory arrest(MHCA,24℃) group,cardiopulmonary bypass(CPB) group and sham operation(SO) group.They were subjected to 80 min hypothermia circulatory arrest,305 min CPB or thoracotomy,respectively.Pick-and-mix custom miRNA real-time PCR panels were utilized to detect intestinal samples.miRNA expression between DHCA and MHCA were compared directly(DHCA vs.MHCA) and indirectly(DHCA/SO vs.MHCA/SO,DHCA/CPB vs.MHCA/CPB).Results Exposure to DHCA caused less intestinal miRNA dysregulation than MHCA.Besides,seven miRNAs(miR-122,miR-145-5p,miR-421-5p,miR-99a,miR-365-5p,miR-31 and miR-192)were differentially expressed between the two hypothermia circulatory arrest groups.Conclusion Better intestinal miRNA protection was provided by DHCA than MHCA.Intestinal miRNA were differentially expressed between hypothermia circulatory arrest at different temperature.

Objective To explore effects of dizocilpine (MK-801) preconditioning on excitatory amino acids and inflammatory response in rats induced by cardiac arrest-cardiopulmonary resuscitation (CACPR).Methods 18 male Sprague Dawley (SD) rats were randomly divided into three groups:control group,CA group and CA + MK-801 group.To establish rat models of CA-CPR and keep samples of serum and specimens of brain tissues for following detection.The injury of neurons was observed by HE staining and expression of N-methyl-D-aspartic acid receptor (NMDAR) in brain tissues was detected by Western blot.The concentrations of interleukin 1 beta (IL-1 β) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA).Results Neurons in CA group were disorganized,cells shrank,nuclei pyknosis,and cytoplasmic eosinophilia,accompanied by inflammatory cell infiltration.Preconditioning with MK-801 reduced the pathological damage of neuron and degree of macrophage infiltration.The relative expression of NMDAR protein in CA group were significantly higher than that in control group (907.9 ±24.9 vs 321.6 ± 18.4,P ＜0.001).Preconditioning with MK-801 significantly decreased the expression of NMDAR in CA + MK-801 group compared with that in CA group (512.4 ± 21.1 vs 907.9 ± 24.9).The CA group showed significantly increased concentrations of IL-1 β and TNF-α than that in control group (P ＜ 0.001),and this effect was abolished by preconditioning with MK-801.CA rats treated with MK-801 showed higher concentrations of IL-1 β and TNF-α than the control group.Conclusions Cardiac arrest causes pathological injury of neurons,up-regulates expression of NMDAR and aggravates inflammatory response.These results induce the apoptosis of nerve cells.Blocking glutamate receptor with MK-801 can inhibit expression of NMDAR,decrease level of cytokines,down-regulate inflammatory reaction degree therefore to protect the brain.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.