It has been confirmed that inflammation plays an important role in the pathogenesis of ischemic stroke. The polarization of microglia as an important participant in the inflammation following stroke is also found to be involved in stroke. This study aimed to investigate the effects of hydrogen gas on the polarization of macrophages/microglia in vitro. Raw264.7 cells were treated with lipopolysaccharides and then exposed to hydrogen. The microglia were treated with the supernatant from oxygen and glucose deprivation-treated neurons and then exposed to hydrogen. The phenotypes of Raw 264.7 cells and microglia were determined by flow cytometry, and cell morphology was observed. Results showed lipopolysaccharides significantly increased the M1 macrophages, and the supernatant from oxygen and glucose deprivation-treated neurons dramatically elevated the proportion of M1 microglia, but both treatments had little influence on the M2 cells. In addition, hydrogen treatment significantly inhibited the increase in M1 cells, but had no influence on M2 ones. Our findings suggest that the neuroprotection of hydrogen may be related to its regulation of microglia in the nervous system after stroke.

Microglia participate in bi-directional control of brain repair after stroke. Previous studies have demonstrated that hydrogen protects brain after ischemia/reperfusion (I/R) by inhibiting inflammation, but the specific mechanism of anti-inflammatory effect of hydrogen is poorly understood. The goal of our study is to investigate whether inhalation of high concentration hydrogen (HCH) is able to attenuate I/R-induced microglia activation. Eighty C57B/L male mice were divided into four groups: sham, I/R, I/R + HCH and I/R + N2/O2 groups. Assessment of animals happened in "blind" matter. I/R was induced by occlusion of middle cerebral artery for one hour). After one hour, filament was withdrawn, which induced reperfusion. Hydrogen treated I/R animals inhaled mix of 66.7% H2 balanced with O2 for 90 minutes, starting immediately after initiation of reperfusion. Control animals (N2/O2) inhaled mix in which hydrogen was replaced with N2 for the same time (90 minutes). The brain injury, such as brain infarction and development of brain edema, as well as neurobehavioral deficits were determined 23 hours after reperfusion. Effect of HCH on microglia activation in the ischemic penumbra was investigated by immunostaining also 23 hours after reperfusion. mRNA expression of inflammation related genes was detected by PCR. Our results showed that HCH attenuated brain injury and consequently reduced neurological dysfunction after I/R. Furthermore, we demonstrated that HCH directed microglia polarization towards anti-inflammatory M2 polarization. This study indicates hydrogen may exert neuroprotective effects by inhibiting the microglial activation and regulating microglial polarization. This study was conducted in agreement with the Animal Care and Use Committee (IACUC) and Institutional Animal Care guidelines regulation (Shanghai Jiao Tong University, China (approval No. A2015-011) in November 2015.

Ischemia-reperfusion (I /R) injury is a crucial pathophysiologic process in the development of various diseases or during organ transplantation. Hydrogen has been widely researched as a potential antioxidant in ischemiareperfusion models of multiple diseases and organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on ischemia-reperfusion injury and organ transplantation. Existing data on the effects and mechanisms of hydrogen on ischemia-reperfusion injury and organ transplantation are specifically reviewed and coupled with further suggestions for future work. In general, a substantial body of experimental evidence suggests that hydrogen significantly has a therapeutic effect on ischemia-reperfusion injury in models of multiple diseases and organ transplantation by inhibiting inflammatory response, oxidative stress and apoptosis through several underlying mechanisms. On this basis, further animal experiments and preliminary human clinical trials regarding the effects of hydrogen on ischemia-reperfusion injury are need to be conducted for the early use of hydrogen as a drug in the clinic.

Senescence has become a hot point issue in recent decades and requires urgent attention. As a novel and effective antioxidant, hydrogen has been proved to alleviate cellular senescence in endothelial cells in vitro. However, the effects and mechanisms of hydrogen on senescence in vivo are still unclear. In the present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow-derived stem cells (BMSCs) were harvested for the detection of hydrogen antisenescence effects and mechanisms. The results showed that the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive cells was reduced in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a better proliferation ability, showed more effectively tri-lineage differentiation potential, and had less percentage of cells in G1 cell cycle arrest than the control cells. Additionally, HRS administration inhibited the production of intracellular reactive oxygen species (ROS) and decreased the expression of senescence-related proteins p53 and p21. Our results revealed that hydrogen could alleviate cellular senescence in vivo. And the underlying mechanism of antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling pathway. Thus, hydrogen could be a new and convenient strategy for alleviating senescence and for therapy of age-related diseases.

It has been confirmed that apoptosis, autophagy and necrosis are the three major modes of cell death. For a long time, necrosis is regarded as a deranged or accidental cell demise. In recent years, there is evidence showing that necrotic cell death can be a well regulated and orchestrated event, which is also known as programmed cell death or “necroptosis”. Necroptosis can be triggered by a variety of external stimuli and regulated by a caspase-independent pathway. It plays a key role in the pathogenesis of some diseases including neurological diseases. In the past two decades, a variety of studies have revealed that the necroptosis related pathway is activated in stroke, and plays a crucial role in the pathogenesis of stroke. Moreover, necroptosis may serve as a potential target in the therapy of stroke because genetic or pharmacological inhibition of necroptosis has been shown to be neuroprotective in stroke in vitro and in vivo. In this review, we briefly summarize re-cent advances in necroptosis, introduce the mechanism and strategies targeting necroptosis in stroke, and finally propose some issues in the treatment of stroke by targeting necroptosis

This study aimed to investigate the role of necroptosis in the neuroprotection of hydrogen in a mouse model of cerebral ischemia/reperfusion (I/R) injury. C57BL mice were randomly divided into sham group, I/R group, hydrogen/oxygen group (HO), nitrogen/oxygen group (NO). Middle cerebral artery occlusion (MCAO) for 1 hour followed by reperfusion was introduced to animals which were allowed to inhale 66.7% hydrogen/33.3% oxygen for 90 minutes since the beginning of reperfusion. Mice in NO group inhaled 66.7% nitrogen/33.3% oxygen. 24 hours after MCAO, brain infarction, brain water content and neurological function were evaluated. The protein expression of mixed lineage kinase domain like protein (MLKL) was detected at 3, 6, 12, 24 and 72 hours after reperfusion in HO group and the protein and mRNA expression of MLKL at 24 hours after MCAO in four groups. Hydrogen inhalation significantly reduced infarct volume, attenuated brain edema and improved neurobehavioral deficit in MCAO mice. The MLKL expression increased after MCAO and peaked at 6–24 hours after reperfusion. However, hydrogen inhalation had no significant effect on the MLKL expression at transcriptional and translational levels after MCAO. This study indicates high concentration hydrogen improves mouse neurological outcome after cerebral I/R injury independent of anti-necroptosis.

Objective To investigate the role of adenosine monophosphate-activated protein kinase (AMPK) and its agonist 5-aminoimidazole-4 carboxamide-ribonucleoside (AICAR) in mice with chronic stress-induced non-alcoholic fatty liver disease (NAFLD).Methods BABL/c mice were randomly divided into control group,stress group,stress plus AICAR group (ST+A group) and AICAR group.The mouse models of chronic stress was established in the stress and ST+A groups,and the mice were injected with AICAR 500 mg/kg in the ST+A and AICAR groups.Before and after treating with AICAR,the levels of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α] and interferon γ [IFN-γ]) in plasma of mice were detected by ELISA,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol,triglyceride and free fatty acid in plasma were determined by automatic biochemical analyzer,the hepatic steatosis was detected by hematoxylin-eosin (H-E) staining and Oil Red O staining,and the expression of AMPK protein in liver tissues was detected by Western blotting.Results Chronic stress caused liver function damage (the levels of ALT and AST were significantly increased,P＜0.01) and liver steatosis in mice,thelevels of pro-inflammatory cytokines (P＜0.05) and free fatty acid (P＜0.01) were significantly increased and the liver AMPK protein expression was significantly decreased (P ＜ 0.01).AICAR improved the liver cell steatosis,and alleviated the changes of above indicators.Conclusion Chronic stress may induce NAFLD through AMPK signaling pathway,and AMPK agonist AICAR can alleviate NAFLD caused by chronic stress.

Objective To investigate the effects ofcorticosterone (CORT) on zinc level in hippocampal HT-22 cells in mice and its potential mechanisms.Methods HT-22 cells were cultured in DMEM and treated with 10μmol/L CORT for 6h.The zinc concentration in cells was measured by a flame atomic absorption spectrophotometer.Real time PCR was performed to determine the mRNA expression levels of MT1,MT3,ZnT1,ZnT3 and ZIP1 in CORT treated HT-22 cells.Results The zinc concentration in CORT-treated HT-22 cells decreased significantly (P＜0.05),which was blocked by glucocorticoid receptor antagonist RU486.Treatment of 10μ mol/L CORT for 6h significantly increased the MT1,MT3,ZIP1,ZnT1 and ZnT3 mRNA expression (P＜0.05).Conclusion CORT could induce zinc dyshomeostasis in HT-22 cells via the regulations of some molecule involved in the uptake,excretion,and intracellular storage or trafficking of zinc.

The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H-2 and 33% O-2) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.

Background and Purpose— Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). Methods— After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. Results— Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood–brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. Conclusions— HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood–brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).

[Objective] To analyze the effects of different educational level,age and body mass index on work ability,and provide scientific basis for improving and maintaining the capability of naval shipboard personnel.[Methods] The work ability index (WAI) scale was used to analyze the work ability of naval shipboard personnel with different educational level,age and body mass index (BMI).[Results] WAI of naval shipboard personnel graduated from university and above,college,senior middle school and technical secondary school were 40.2±5.8,39.2±6.7,40.4±5.8 respectively,which were all higher than who graduated from junior high school (30.7-±7.1).Naval shipboard personnel graduated from junior high school showed middle work ability,while naval shipboard personnel graduated from technical secondary school and above showed good work ability.WAI of naval shipboard personnel was negatively correlated with age (r=--0.12) and BMI (r=--0.08).[Conclusion] The work ability of naval shipboard personnel graduated from junior high school need to be improved.Jobs should be assigned according to different age and BMI,which is helpful to improve the work ability of naval shipboard personnel.

Background and aims: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism.Methods: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R + HCH, LY294002 (PI3K inhibitor) + I/R + HCH, and LY + I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1 h immediately after surgery. LY294002 was intravenously injected at 10 mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A(2A) receptor, additional four groups were included: ZM241385 (A2A receptor antagonist) + I/R + HCH, ZM241385 + I/R, bpv(HOpic) (PTEN inhibitor) + I/R, and ZM241385 + bpv + I/R + HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A(2A) receptor in this protection.Results: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic).Conclusion: Our findings indicate that HCH may protect the liver against I/R injury through the A(2A) dependent PI3K-Akt pathway. (C) 2017 Elsevier Inc. All rights reserved.

Carbon monoxide (CO) is known as a toxic gas. Although there have been many studies on both toxic and protective effects of CO, most of these studies lack novelty, except for Eng H Lo team's study on the therapeutic effect of CO on brain injuries. In this commentary, we summarize the potential application value of CO in the treatment of some clinical diseases, especially its protective effect and nerve regeneration in brain injuries, hoping that our interest in CO could promote related clinical application studies.

Herein, we develop a novel method for designing electrochemical biosensors with both current and potential signal outputs for the simultaneous determination of two species in a living system. Oxygen (O2 ) and pH, simple and very important species, are employed as model molecules. By designing and synthesizing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous detection and ratiometric quantification of O2 and pH in the brain. The reduction peak current of the hemin group increases with the concentration of O2 from 1.3 to 200.6 μm. Meanwhile, the peak potential positively shifts with decreasing pH from 8.0 to 5.5, resulting in the simultaneous determination of O2 and pH. The Fc group can serve as an internal reference for ratiometric biosensing because its current and potential signals remain almost constant with variations of O2 and pH. The developed biosensor has high temporal and spatial resolutions, as well as remarkable selectivity and accuracy, and is successfully applied in the real-time quantification of O2 and pH in the brain upon ischemia, as well as in tumor during cancer therapy.

Stroke is a cerebrovascular disease with high mortality and morbidity. Despite extensive research, there are only a very limited number of therapeutic approaches suitable for treatment of stroke patients as yet. Mounting evidence has demonstrated that such gases as oxygen, hydrogen and hydrogen sulfide are able to provide neuroprotection after stroke. In this paper, we will focus on the recent two years' progress in the development of gas therapies of stroke and in understanding the molecular mechanisms underlying protection induced by medical gases. We will also discuss the advantages and challenges of these approaches and provide information for future study.

目的 通过对舰艇员的工作能力进行调查,了解舰艇员的工作能力现状,为提高和维护舰艇员作业能力提供科学依据.方法 用工作能力指数(work ability index,WAI)量表对759名舰艇员的工作能力进行调查.结果 759名舰艇员WAI平均得分为(38.47±7.44)分,工作能力分级为“工作能力好”.但仍有32.6％舰艇员工作能力分级处于工作能力弱或中等.结论 相当比例舰艇员工作能力处于弱或中等,应进行修复和提高.

为保卫海洋国土利益以及保障海洋战略的顺利实施,海军战斗力提升成为我国当下面临的紧迫任务. 保障海军基层官兵的健康状态,是保障和提升海军战斗力的必要条件,而基层军医的医疗技能水平直接决定了海军战斗力保障及服务质量. 笔者对海军基层军医职业发展存在的问题及对策进行初步探讨,现报道如下.

目的 了解舰员对舰艇舱室空气品质的主观评价,为今后改善空气品质提供实验依据.方法 随机抽取海军某舰舰员80名,采用“室内空气品质主观评价调查表”对该舰舰员进行空气品质的主观评价调查.结果 舰员对舱室工作环境普遍评价较差,其中对空气品质评价为“较差”或者“很差”的占62.8％,舰员对舱室内空气的不接受率为74.1％,不满意率达到80.5％,在所调查的症状中,舱室内舰员发生率普遍较高,多数均在30％以上.结论 舰员对舰艇舱室内空气品质主观评价普遍较差,并且影响着舰员的身心健康.

Depression is a common psychopathological disorders. Studies of depression have indicated that zinc play a role in the depression pathophysiology and treatment. In present study, we examined the effects of zinc and imipramine supplement alone or combination of zinc and imipramine in mice induced by chronic restraint stress (CRS). Moreover, the possible roles of zinc receptor (G protein-coupled receptor 39, GPR39)-related pathway was investigated. Decreased weight and increased corticosterone (CORT) were observed after 3 weeks CRS exposure. It was shown that CRS induced lower serum zinc, higher hippocampal zinc, increased immobility time in tail suspension test and decreased movement distance in spontaneous activity test, which could be normalized by zinc (30 mg/kg) and imipramine (20 mg/kg) supplement alone and combination of zinc (15 mg/kg) and imipramine (5 mg/kg) for 3 weeks after CRS exposure. Moreover, the changes in mRNA expressions of GPR39, cAMP-response element binding protein (CREB), brain-derived neurotropic factor (BDNF) and n-methytl-d-aspartate receptors (NMDAR) could be reversed by the same treatment mentioned above. These results suggested that zinc dyshomeostasis in serum and hippocampus and depression-like behavior in CRS exposure animals observed in present study could be normalized by zinc and imipramine. The combination of zinc and imipramine in low dose has synergetic effects. The possible mechanism might be correlated to GPR39 receptor-related pathway.

随着社会和经济的发展，人们对营养与疾病的关系以及食品安全等问题越来越关注。为适应新的社会发展需求，培养具有解决实际问题能力的高素质医学人才，提高营养与食品卫生学的教学质量，对该课程的教学内容进行精炼和更新，使其更贴近社会，与时俱进。采用案例式、辩论式和现场教学等多种手段，充分发挥学员学习的主观能动性，同时对实践教学尝试实行新模式，采用研究型实验教学方法，进一步提升学员的创新精神和科研能力。